Summary: A type of extracellularly deposited substance composed of an amyloid protein and additional components including HEPARAN SULFATE PROTEOGLYCAN; LAMININ; COLLAGEN TYPE IV; SERUM AMYLOID P-COMPONENT; and APOLIPOPROTEINS E which together form characteristic amyloid fibrils. The core of amyloid fibrils is formed by the stacking of overlapping beta-pleated sheet domains of the amyloid protein. There are many different amyloid proteins that have been found forming the core of the fibrils in vivo. However, amyloid can be formed from any protein that exposes beta-pleated strand conformations during unfolding or refolding. A common characteristic of amyloid is the ability to bind such dyes as CONGO RED and thioflavine.

Top Publications

  1. ncbi Protein misfolding, functional amyloid, and human disease
    Fabrizio Chiti
    Dipartimento di Scienze Biochimiche, Universita degli Studi di Firenze, I 50134 Firenze, Italy
    Annu Rev Biochem 75:333-66. 2006
  2. ncbi Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
    Rakez Kayed
    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 3900, USA
    Science 300:486-9. 2003
  3. ncbi Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B
    William E Klunk
    Department of Psychiatry, PET Facility, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213 2582, USA
    Ann Neurol 55:306-19. 2004
  4. pmc Amyloid plaque core protein in Alzheimer disease and Down syndrome
    C L Masters
    Proc Natl Acad Sci U S A 82:4245-9. 1985
  5. ncbi Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein
    G G Glenner
    Biochem Biophys Res Commun 120:885-90. 1984
  6. pmc Atomic view of a toxic amyloid small oligomer
    Arthur Laganowsky
    Department of Biological Chemistry, University of California Los Angeles UCLA, Howard Hughes Medical Institute HHMI, Los Angeles, CA 90095, USA
    Science 335:1228-31. 2012
  7. ncbi Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes
    Alexandra E Butler
    Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Diabetes 52:102-10. 2003
  8. pmc Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes
    Seth L Masters
    Immunology Research Centre, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland
    Nat Immunol 11:897-904. 2010
  9. pmc 3D structure of Alzheimer's amyloid-beta(1-42) fibrils
    Thorsten Luhrs
    The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 102:17342-7. 2005
  10. pmc The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis
    Jixi Li
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Cell 150:339-50. 2012

Detail Information

Publications357 found, 100 shown here

  1. ncbi Protein misfolding, functional amyloid, and human disease
    Fabrizio Chiti
    Dipartimento di Scienze Biochimiche, Universita degli Studi di Firenze, I 50134 Firenze, Italy
    Annu Rev Biochem 75:333-66. 2006
    ..We review recent advances toward the elucidation of the structures of amyloid fibrils and the mechanisms of their formation at a molecular level...
  2. ncbi Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
    Rakez Kayed
    Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 3900, USA
    Science 300:486-9. 2003
    ..Soluble oligomers have a unique distribution in human AD brain that is distinct from fibrillar amyloid. These results indicate that different types of soluble amyloid oligomers have a common structure and suggest ..
  3. ncbi Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B
    William E Klunk
    Department of Psychiatry, PET Facility, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213 2582, USA
    Ann Neurol 55:306-19. 2004
    This report describes the first human study of a novel amyloid-imaging positron emission tomography (PET) tracer, termed Pittsburgh Compound-B (PIB), in 16 patients with diagnosed mild AD and 9 controls...
  4. pmc Amyloid plaque core protein in Alzheimer disease and Down syndrome
    C L Masters
    Proc Natl Acad Sci U S A 82:4245-9. 1985
    We have purified and characterized the cerebral amyloid protein that forms the plaque core in Alzheimer disease and in aged individuals with Down syndrome...
  5. ncbi Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein
    G G Glenner
    Biochem Biophys Res Commun 120:885-90. 1984
    ..This protein may be derived from a unique serum precursor which may provide a diagnostic test for Alzheimer's disease and a means to understand its pathogenesis...
  6. pmc Atomic view of a toxic amyloid small oligomer
    Arthur Laganowsky
    Department of Biological Chemistry, University of California Los Angeles UCLA, Howard Hughes Medical Institute HHMI, Los Angeles, CA 90095, USA
    Science 335:1228-31. 2012
    b>Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form...
  7. ncbi Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes
    Alexandra E Butler
    Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Diabetes 52:102-10. 2003
  8. pmc Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes
    Seth L Masters
    Immunology Research Centre, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland
    Nat Immunol 11:897-904. 2010
    ..Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the ..
  9. pmc 3D structure of Alzheimer's amyloid-beta(1-42) fibrils
    Thorsten Luhrs
    The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 102:17342-7. 2005
    Alzheimer's disease is the most fatal neurodegenerative disorder wherein the process of amyloid-beta (Abeta) amyloidogenesis appears causative...
  10. pmc The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis
    Jixi Li
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Cell 150:339-50. 2012
    ..Structured amyloid cores are mapped in RIP1 and RIP3 that are flanked by regions of mobility...
  11. pmc Prion-like transmission of protein aggregates in neurodegenerative diseases
    Patrik Brundin
    Patrik Brundin is at the Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund University, BMC A10, 221 84 Lund, Sweden
    Nat Rev Mol Cell Biol 11:301-7. 2010
    ..The transfer of naked infectious particles between cells could therefore be a target for new disease-modifying therapies...
  12. pmc Structure of the cross-beta spine of amyloid-like fibrils
    Rebecca Nelson
    Howard Hughes Medical Institute, UCLA DOE Institute for Genomics and Proteomics, Box 951570, UCLA, Los Angeles, California 90095 1570, USA
    Nature 435:773-8. 2005
    Numerous soluble proteins convert to insoluble amyloid-like fibrils that have common properties. Amyloid fibrils are associated with fatal diseases such as Alzheimer's, and amyloid-like fibrils can be formed in vitro...
  13. ncbi Atomic structures of amyloid cross-beta spines reveal varied steric zippers
    Michael R Sawaya
    Howard Hughes Medical Institute, UCLA DOE Institute of Genomics and Proteomics, Los Angeles, California 90095 1570, USA
    Nature 447:453-7. 2007
    b>Amyloid fibrils formed from different proteins, each associated with a particular disease, contain a common cross-beta spine...
  14. ncbi EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers
    Dagmar E Ehrnhoefer
    Max Delbrueck Center for Molecular Medicine, AG Neuroproteomics, 13092 Berlin, Germany
    Nat Struct Mol Biol 15:558-66. 2008
    The accumulation of beta-sheet-rich amyloid fibrils or aggregates is a complex, multistep process that is associated with cellular toxicity in a number of human protein misfolding disorders, including Parkinson's and Alzheimer's diseases...
  15. ncbi The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
    J Kang
    Nature 325:733-6. 1987
    Alzheimer's disease is characterized by a widespread functional disturbance of the human brain. Fibrillar amyloid proteins are deposited inside neurons as neurofibrillary tangles and extracellularly as amyloid plaque cores and in blood ..
  16. pmc Amyloid precursor protein trafficking, processing, and function
    Gopal Thinakaran
    Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 283:29615-9. 2008
    Intracellular trafficking and proteolytic processing of amyloid precursor protein (APP) have been the focus of numerous investigations over the past two decades...
  17. ncbi Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions
    Heidi Olzscha
    Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany
    Cell 144:67-78. 2011
    ..Here, we have analyzed the gain-of-function toxicity of artificial β sheet proteins that were designed to form amyloid-like fibrils...
  18. pmc Identifying the amylome, proteins capable of forming amyloid-like fibrils
    Lukasz Goldschmidt
    Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095 1570, USA
    Proc Natl Acad Sci U S A 107:3487-92. 2010
    The amylome is the universe of proteins that are capable of forming amyloid-like fibrils. Here we investigate the factors that enable a protein to belong to the amylome...
  19. ncbi Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory
    Randy L Buckner
    Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63105, USA
    J Neurosci 25:7709-17. 2005
    Alzheimer's disease (AD) and antecedent factors associated with AD were explored using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies...
  20. pmc A systematic survey identifies prions and illuminates sequence features of prionogenic proteins
    Simon Alberti
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 137:146-58. 2009
    ..The self-perpetuating states of these proteins present a vast source of heritable phenotypic variation that increases the adaptability of yeast populations to diverse environments...
  21. ncbi Islet amyloid polypeptide, islet amyloid, and diabetes mellitus
    Per Westermark
    Department of Medical Cell Biology and Immunology, Uppsala University, Uppsala, Sweden
    Physiol Rev 91:795-826. 2011
    Islet amyloid polypeptide (IAPP, or amylin) is one of the major secretory products of β-cells of the pancreatic islets of Langerhans...
  22. ncbi Exploring the sequence determinants of amyloid structure using position-specific scoring matrices
    Sebastian Maurer-Stroh
    VIB Switch Laboratory, Flanders Institute for Biotechnology and Vrije Universiteit Brussel, Brussels, Belgium
    Nat Methods 7:237-42. 2010
    ..results in beta-sheet-like assemblies that adopt either a variety of amorphous morphologies or ordered amyloid-like structures...
  23. ncbi The transcellular spread of cytosolic amyloids, prions, and prionoids
    Adriano Aguzzi
    Institute of Neuropathology, University Hospital of Zurich, Schmelzbergstrasse 12, CH 8091 Zurich, Switzerland
    Neuron 64:783-90. 2009
  24. pmc Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade
    Christine E Bulawa
    Pfizer Orphan and Genetic Diseases Research Unit, Cambridge, MA 02140, USA
    Proc Natl Acad Sci U S A 109:9629-34. 2012
    ..facilitate tetramer dissociation, monomer misfolding, and aggregation, although wild-type TTR can also form amyloid fibrils in elderly patients...
  25. pmc Functional amyloids as natural storage of peptide hormones in pituitary secretory granules
    Samir K Maji
    Laboratory of Physical Chemistry, Eidgenossische Technische Hochschule ETH Zurich, Wolfgang Paulistrasse 10, CH 8093 Zurich, Switzerland
    Science 325:328-32. 2009
    ..a normal biological function, as demonstrated by fungal prions, which are involved in prion replication, and the amyloid protein Pmel17, which is involved in mammalian skin pigmentation...
  26. ncbi Amyloid formation by globular proteins under native conditions
    Fabrizio Chiti
    Dipartimento di Scienze Biochimiche, Universita degli Studi di Firenze, Viale Morgagni 50, I 50134 Firenze, Italy
    Nat Chem Biol 5:15-22. 2009
    ..We review recent evidence on this topic and discuss its significance for understanding the onset and potential inhibition of protein aggregation in the context of diseases...
  27. ncbi A diversity of assembly mechanisms of a generic amyloid fold
    Timo Eichner
    Astbury Centre for Structural Molecular Biology and Institute of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK
    Mol Cell 43:8-18. 2011
    Protein misfolding and amyloid assembly have long been recognized as being responsible for many devastating human diseases...
  28. ncbi The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse
    G P Lim
    Departments of Medicine and Neurology, University of California, Los Angeles, Los Angeles, California 90095, USA
    J Neurosci 21:8370-7. 2001
    ..With low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble beta-amyloid (Abeta), soluble Abeta, and plaque burden were significantly decreased by 43-50%...
  29. ncbi Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695
    M A Chishti
    Centre for Research in Neurodegenerative Diseases, The Department of Laboratory Medicine, Division of Neurology, University Health Network, University of Toronto, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 276:21562-70. 2001
    ..transgenic (Tg) models by exploiting the synergistic effects of familial Alzheimer's disease mutations on amyloid beta-peptide (Abeta) biogenesis...
  30. ncbi Small-molecule conversion of toxic oligomers to nontoxic β-sheet-rich amyloid fibrils
    Jan Bieschke
    Neuroproteomics, Max Delbrueck Center for Molecular Medicine, Berlin, Germany
    Nat Chem Biol 8:93-101. 2012
    Several lines of evidence indicate that prefibrillar assemblies of amyloid-β (Aβ) polypeptides, such as soluble oligomers or protofibrils, rather than mature, end-stage amyloid fibrils cause neuronal dysfunction and memory impairment ..
  31. ncbi Functional amyloid--from bacteria to humans
    Douglas M Fowler
    Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Trends Biochem Sci 32:217-24. 2007
    b>Amyloid--a fibrillar, cross beta-sheet quaternary structure--was first discovered in the context of human disease and tissue damage, and was thought to always be detrimental to the host...
  32. pmc In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18)
    Dean F Wong
    Division of Nuclear Medicine, Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287 0807, USA
    J Nucl Med 51:913-20. 2010
    An (18)F-labeled PET amyloid-beta (Abeta) imaging agent could facilitate the clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer disease (AD) pathology...
  33. pmc EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity
    Jan Bieschke
    Max Delbrueck Center for Molecular Medicine, Robert Roessle Strasse 10, 13125 Berlin Buch, Germany
    Proc Natl Acad Sci U S A 107:7710-5. 2010
    Protein misfolding and formation of beta-sheet-rich amyloid fibrils or aggregates is related to cellular toxicity and decay in various human disorders including Alzheimer's and Parkinson's disease...
  34. pmc Amyloid ion channels: a common structural link for protein-misfolding disease
    Arjan Quist
    Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA
    Proc Natl Acad Sci U S A 102:10427-32. 2005
    ..and Parkinson's diseases, result from protein misfolding, giving a distinct fibrillar feature termed amyloid. Recent studies show that only the globular (not fibrillar) conformation of amyloid proteins is sufficient to ..
  35. ncbi Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease
    Hiroaki Fukumoto
    Alzheimer Disease Research Unit, Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital East, Bldg 114, Room 2010, 114 16th Street, Charlestown, MA 02129, USA
    Arch Neurol 59:1381-9. 2002
    b>Amyloid plaques, a major pathological feature of Alzheimer disease (AD), are composed of an internal fragment of amyloid precursor protein (APP): the 4-kd amyloid-beta protein (Abeta)...
  36. pmc Role of phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) in intracellular amyloid precursor protein (APP) processing and amyloid plaque pathogenesis
    Qingli Xiao
    Hope Center for Neurological Disorders and Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 287:21279-89. 2012
    One of the pathological hallmarks of Alzheimer disease is the accumulation of amyloid plaques in the extracellular space in the brain...
  37. pmc Antiparallel β-sheet architecture in Iowa-mutant β-amyloid fibrils
    Wei Qiang
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0520, USA
    Proc Natl Acad Sci U S A 109:4443-8. 2012
    Wild-type, full-length (40- and 42-residue) amyloid β-peptide (Aβ) fibrils have been shown by a variety of magnetic resonance techniques to contain cross-β structures in which the β-sheets have an in-register parallel supramolecular ..
  38. pmc Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism
    Samuel I A Cohen
    Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom
    Proc Natl Acad Sci U S A 110:9758-63. 2013
    The generation of toxic oligomers during the aggregation of the amyloid-β (Aβ) peptide Aβ42 into amyloid fibrils and plaques has emerged as a central feature of the onset and progression of Alzheimer's disease, but the molecular ..
  39. pmc Amyloid in neurodegenerative diseases: friend or foe?
    Katie J Wolfe
    Department of Cell and Developmental Biology, School of Medicine, University of North Carolina at Chapel Hill, 107 Mason Farm Road, Chapel Hill, NC 27514, United States
    Semin Cell Dev Biol 22:476-81. 2011
    Accumulation of amyloid-like aggregates is a hallmark of numerous neurodegenerative disorders such as Alzheimer's and polyglutamine disease...
  40. pmc Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease
    Jia Yao
    Department of Pharmacology and Pharmaceutical Sciences and Program in Neuroscience, Pharmaceutical Sciences Center, University of Southern California, Los Angeles, CA 90033, USA
    Proc Natl Acad Sci U S A 106:14670-5. 2009
    ..Mitochondrial amyloid beta (Abeta) level in the 3xTg-AD mice was significantly increased at 9 months and temporally correlated with ..
  41. ncbi Oligomeric intermediates in amyloid formation: structure determination and mechanisms of toxicity
    Marcus Fändrich
    Max Planck Research Unit for Enzymology of Protein Folding and Martin Luther University Halle Wittenberg, Weinbergweg 22, 01620 Halle Saale, Germany
    J Mol Biol 421:427-40. 2012
    Oligomeric intermediates are non-fibrillar polypeptide assemblies that occur during amyloid fibril formation and that are thought to underlie the aetiology of amyloid diseases, such as Alzheimer's disease, Parkinson's disease and ..
  42. ncbi Inhibition of amyloid formation
    Torleif Härd
    Department of Molecular Biology, Swedish University of Agricultural Sciences, SE 751 24 Uppsala, Sweden
    J Mol Biol 421:441-65. 2012
    b>Amyloid is aggregated protein in the form of insoluble fibrils. Amyloid deposition in human tissue-amyloidosis-is associated with a number of diseases including all common dementias and type II diabetes...
  43. pmc Operational plasticity enables hsp104 to disaggregate diverse amyloid and nonamyloid clients
    Morgan E Desantis
    Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cell 151:778-93. 2012
    ..adapt different mechanisms of intersubunit collaboration to disaggregate stress-induced aggregates versus amyloid. To resolve disordered aggregates, Hsp104 subunits collaborate noncooperatively via probabilistic substrate ..
  44. pmc Amyloid triggers extensive cerebral angiogenesis causing blood brain barrier permeability and hypervascularity in Alzheimer's disease
    Kaan E Biron
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
    PLoS ONE 6:e23789. 2011
    ..Cerebrovascular integrity was characterized in Tg2576 AD model mice that overexpress the human amyloid precursor protein (APP) containing the double missense mutations, APPsw, found in a Swedish family, that causes ..
  45. ncbi Mechanism of amyloidogenesis: nucleation-dependent fibrillation versus double-concerted fibrillation
    Ghibom Bhak
    School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Seoul, Korea
    BMB Rep 42:541-51. 2009
    ..defines a condition in which a soluble and innocuous protein turns to insoluble protein aggregates known as amyloid fibrils...
  46. ncbi Nucleated conformational conversion and the replication of conformational information by a prion determinant
    T R Serio
    Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA
    Science 289:1317-21. 2000
    ..The critical region of one prion protein, Sup35, is initially unstructured in solution and then forms self-seeded amyloid fibers. We examined in vitro the mechanism by which this state is attained and replicated...
  47. pmc Sequence determinants of amyloid fibril formation
    Manuela Lopez de la Paz
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Proc Natl Acad Sci U S A 101:87-92. 2004
    The establishment of rules that link sequence and amyloid feature is critical for our understanding of misfolding diseases...
  48. ncbi The PASTA server for protein aggregation prediction
    Antonio Trovato
    Department of Physics G Galilei, University of Padova, Padova, Italy
    Protein Eng Des Sel 20:521-3. 2007
    Many different proteins aggregate into amyloid fibrils characterized by cross-beta structure. beta-strands contributed by distinct protein molecules are generally found in a parallel in-register alignment...
  49. pmc Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance
    Tristan Bolmont
    Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, D 72076 Tubingen, Germany
    J Neurosci 28:4283-92. 2008
    Microglial cells aggregate around amyloid plaques in Alzheimer's disease, but, despite their therapeutic potential, various aspects of their reactive kinetics and role in plaque pathogenesis remain hypothetical...
  50. ncbi An analytical solution to the kinetics of breakable filament assembly
    Tuomas P J Knowles
    Cavendish Laboratory, University of Cambridge, J J Thomson Avenue, Cambridge CB3 0HE, UK
    Science 326:1533-7. 2009
    ..Application to the case of protein aggregation demonstrates that the kinetics of amyloid growth can often be dominated by secondary rather than by primary nucleation events...
  51. pmc Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β
    Justin M Nussbaum
    Department of Biology, University of Virginia, Charlottesville, Virginia 22904, USA
    Nature 485:651-5. 2012
    Extracellular plaques of amyloid-β and intraneuronal neurofibrillary tangles made from tau are the histopathological signatures of Alzheimer's disease...
  52. ncbi Biology of amyloid: structure, function, and regulation
    Jason Greenwald
    ETH Zurich, Physical Chemistry, ETH Honggerberg, 8093 Zurich, Switzerland
    Structure 18:1244-60. 2010
    ..It grows by recruitment of the corresponding amyloid protein, while its repetitiveness can translate what would be a nonspecific activity as monomer into a potent one ..
  53. pmc Iron promotes the toxicity of amyloid beta peptide by impeding its ordered aggregation
    Beinan Liu
    Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust Medical Research Council Building, Hills Road, Cambridge CB2 0XY, United Kingdom
    J Biol Chem 286:4248-56. 2011
    ..previously shown that overexpressing subunits of the iron-binding protein ferritin can rescue the toxicity of the amyloid β (Aβ) peptide in our Drosophila model system...
  54. ncbi Alzheimer's dementia begins as a disease of small blood vessels, damaged by oxidative-induced inflammation and dysregulated amyloid metabolism: implications for early detection and therapy
    Vincent T Marchesi
    Department of Pathology, Boyer Center for Molecular Medicine, Yale University, 295 Congress Ave, P O Box 9812, New Haven, CT 06536 0812, USA
    FASEB J 25:5-13. 2011
    There is a widely shared view among Alzheimer's disease (AD) investigators that the amyloid hypothesis best describes the pathogenic cascade that leads, ultimately, to neuronal degeneration and irreversible dementia...
  55. pmc The contrasting effect of macromolecular crowding on amyloid fibril formation
    Qian Ma
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China
    PLoS ONE 7:e36288. 2012
    b>Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms...
  56. ncbi FoldAmyloid: a method of prediction of amyloidogenic regions from protein sequence
    Sergiy O Garbuzynskiy
    Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia
    Bioinformatics 26:326-32. 2010
    Amyloidogenic regions in polypeptide chains are very important because such regions are responsible for amyloid formation and aggregation. It is useful to be able to predict positions of amyloidogenic regions in protein chains.
  57. ncbi Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution
    Massimo Stefani
    Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy
    J Mol Med (Berl) 81:678-99. 2003
    The deposition of proteins in the form of amyloid fibrils and plaques is the characteristic feature of more than 20 degenerative conditions affecting either the central nervous system or a variety of peripheral tissues...
  58. ncbi Critical role of amyloid-like oligomers of Drosophila Orb2 in the persistence of memory
    Amitabha Majumdar
    Stowers Institute for Medical Research, Kansas City, MO 64110, USA
    Cell 148:515-29. 2012
    ..Here, we found that the Drosophila CPEB Orb2 forms amyloid-like oligomers, and oligomers are enriched in the synaptic membrane fraction...
  59. pmc Opposing effects of glutamine and asparagine govern prion formation by intrinsically disordered proteins
    Randal Halfmann
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Mol Cell 43:72-84. 2011
    ..A systematic survey of prion-forming domains suggested that Q and N residues have distinct effects on amyloid formation...
  60. pmc Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation
    Lynette Cegelski
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Chem Biol 5:913-9. 2009
    Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae...
  61. ncbi Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans
    Anne M Fagan
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 59:512-9. 2006
    b>Amyloid-beta(42) (Abeta(42)) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Abeta(42) is decreased in dementia of the Alzheimer's type...
  62. pmc Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation
    Stuart A Sievers
    Department of Biological Chemistry, Howard Hughes Medical Institute, UCLA, Box 951970, Los Angeles, California 90095 1570, USA
    Nature 475:96-100. 2011
    Many globular and natively disordered proteins can convert into amyloid fibrils. These fibrils are associated with numerous pathologies as well as with normal cellular functions, and frequently form during protein denaturation...
  63. pmc Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients
    G J Cooper
    Department of Biochemistry, University of Oxford, United Kingdom
    Proc Natl Acad Sci U S A 84:8628-32. 1987
    Deposition of amyloid in pancreatic islets is a common feature in human type 2 diabetic subjects but because of its insolubility and low tissue concentrations, the structure of its monomer has not been determined...
  64. pmc Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan
    Silvestre Alavez
    Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, California 94945, USA
    Nature 472:226-9. 2011
    ..A group of small molecules, traditionally used in histopathology to stain amyloid in tissues, bind protein fibrils and slow aggregation in vitro and in cell culture...
  65. pmc Frequent amyloid deposition without significant cognitive impairment among the elderly
    Howard Jay Aizenstein
    Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Arch Neurol 65:1509-17. 2008
    To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, ..
  66. ncbi Conformational constraints for amyloid fibrillation: the importance of being unfolded
    Vladimir N Uversky
    Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA
    Biochim Biophys Acta 1698:131-53. 2004
    Recent reports give strong support to the idea that amyloid fibril formation and the subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins...
  67. ncbi Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus
    A Lorenzo
    Department of Neurology, Harvard Medical School, Boston, Massachusetts
    Nature 368:756-60. 1994
    The 37-amino-acid polypeptide amylin is the principal constituent of the amyloid deposits that form in the islets of Langerhans in patients with type-2 diabetes mellitus, but its role in the pathogenesis of this disease is unresolved...
  68. ncbi A toxic monomeric conformer of the polyglutamine protein
    Yoshitaka Nagai
    Division of Clinical Genetics, Department of Medical Genetics, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
    Nat Struct Mol Biol 14:332-40. 2007
    ..conformational transition of the expanded polyQ protein monomer precedes its assembly into beta-sheet-rich amyloid-like fibrils...
  69. pmc Annular protofibrils are a structurally and functionally distinct type of amyloid oligomer
    Rakez Kayed
    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
    J Biol Chem 284:4230-7. 2009
    b>Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases...
  70. ncbi A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model
    Giselle P Lim
    Department of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA
    J Neurosci 25:3032-40. 2005
    ..are unknown, we used the APPsw (Tg2576) transgenic mouse model to evaluate the impact of dietary DHA on amyloid precursor protein (APP) processing and amyloid burden...
  71. pmc Amyloid fibers provide structural integrity to Bacillus subtilis biofilms
    Diego Romero
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:2230-4. 2010
    ..analyses, in combination with the use of specific dyes and microscopic analyses, indicate that TasA forms amyloid fibers. Consistent with this hypothesis, TasA fibers required harsh treatments (e.g...
  72. pmc The role of microglia in amyloid clearance from the AD brain
    C Y Daniel Lee
    School of Medicine, Case Western Reserve University, SOM E649, 10900 Euclid Avenue, Cleveland, OH 44106 4928, USA
    J Neural Transm 117:949-60. 2010
    ..the most prominent cause of senile dementia, is clinically characterized by the extracellular deposition of beta-amyloid (Abeta) and the intracellular neurofibrillary tangles...
  73. pmc Amyloidogenic determinants are usually not buried
    Kimon K Frousios
    Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 15701, Greece
    BMC Struct Biol 9:44. 2009
    ..are a group of usually fatal diseases, probably caused by protein misfolding and subsequent aggregation into amyloid fibrillar deposits...
  74. pmc Functional amyloid formation within mammalian tissue
    Douglas M Fowler
    Department of Chemistry, The Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
    PLoS Biol 4:e6. 2006
    b>Amyloid is a generally insoluble, fibrous cross-beta sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease...
  75. ncbi Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct
    Mihaela Necula
    Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA
    J Biol Chem 282:10311-24. 2007
    Alzheimer disease is characterized by the abnormal aggregation of amyloid beta peptide into extracellular fibrillar deposits known as amyloid plaques...
  76. ncbi Gender and genetic background effects on brain metal levels in APP transgenic and normal mice: implications for Alzheimer beta-amyloid pathology
    Christa J Maynard
    Department of Pathology, The University of Melbourne, VIC 3010, Australia
    J Inorg Biochem 100:952-62. 2006
    The incidence of Alzheimer's disease (AD) is greater in women than men at any age, as is the development of amyloid pathology in several transgenic mouse models of AD...
  77. ncbi Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers
    James Shorter
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 304:1793-7. 2004
    The protein-remodeling factor Hsp104 governs inheritance of [PSI+], a yeast prion formed by self-perpetuating amyloid conformers of the translation termination factor Sup35...
  78. ncbi The physical basis of how prion conformations determine strain phenotypes
    Motomasa Tanaka
    Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California San Francisco and California Institute for Quantitative Biomedical Research, San Francisco, California 94143, USA
    Nature 442:585-9. 2006
    ..conformations of yeast Sup35 (the [PSI+] protein determinant) and their in vivo phenotypes reveals that the Sup35 amyloid causing the strongest phenotype surprisingly shows the slowest growth...
  79. pmc A method for probing the mutational landscape of amyloid structure
    Charles W O'Donnell
    Computer Science and Artificial Intelligence Laboratory, Cambridge, MA 02139, USA
    Bioinformatics 27:i34-42. 2011
    Proteins of all kinds can self-assemble into highly ordered β-sheet aggregates known as amyloid fibrils, important both biologically and clinically...
  80. pmc Out-of-register β-sheets suggest a pathway to toxic amyloid aggregates
    Cong Liu
    UCLA DOE Institute for Genomics and Proteomics, The Howard Hughes Medical Institute, Molecular Biology Institute and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 109:20913-8. 2012
    Although aberrant protein aggregation has been conclusively linked to dozens of devastating amyloid diseases, scientists remain puzzled about the molecular features that render amyloid fibrils or small oligomers toxic...
  81. ncbi The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-β(1-40) peptide
    Priyanka Narayan
    Department of Chemistry, University of Cambridge, Cambridge, UK
    Nat Struct Mol Biol 19:79-83. 2012
    ..We have examined the interactions between human clusterin and the Alzheimer's disease-associated amyloid-β(1-40) peptide (Aβ(1-40)), which is prone to aggregate into an ensemble of oligomeric intermediates implicated ..
  82. pmc Highly efficient protein misfolding cyclic amplification
    Nuria Gonzalez-Montalban
    Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, Maryland, United States of America
    PLoS Pathog 7:e1001277. 2011
    ..The new PMCAb format offers immediate practical benefits and opens new avenues for developing fast ultrasensitive assays and for producing abundant quantities of PrP(Sc)in vitro...
  83. ncbi Lipid membranes modulate the structure of islet amyloid polypeptide
    Sajith A Jayasinghe
    Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, University of Southern California, 1501 San Pablo Street, Los Angeles, California 90033, USA
    Biochemistry 44:12113-9. 2005
    The 37-residue islet amyloid polypeptide (IAPP) is thought to play an important role in the pathogenesis of type II diabetes...
  84. pmc Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits
    Robert Tamayev
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 107:20822-7. 2010
    According to the prevailing "amyloid cascade hypothesis," genetic dementias such as Alzheimer's disease and familial Danish dementia (FDD) are caused by amyloid deposits that trigger tauopathy, neurodegeneration, and behavioral/cognitive ..
  85. ncbi Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committee of the International Society of Amyloidosis
    Jean D Sipe
    Department of Biochemistry Emerita, Boston University School of Medicine, Boston, MA 02118, USA
    Amyloid 17:101-4. 2010
    A system of amyloid fibril nomenclature based on the chemical identity of the amyloid fibril forming protein is recommended...
  86. ncbi Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins
    D R Borchelt
    Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
    Neuron 19:939-45. 1997
    ..of experimental in vitro and in vivo settings, FAD-linked presenilin variants influence the processing of the amyloid precursor protein (APP), leading to elevated levels of the highly fibrillogenic Abeta1-42 peptides that are ..
  87. ncbi Amyloid fibrils of the HET-s(218-289) prion form a beta solenoid with a triangular hydrophobic core
    Christian Wasmer
    Physical Chemistry, ETH Zurich, 8093 Zurich, Switzerland
    Science 319:1523-6. 2008
    ..We present a structural model based on solid-state nuclear magnetic resonance restraints for amyloid fibrils from the prion-forming domain (residues 218 to 289) of the HET-s protein from the filamentous fungus ..
  88. ncbi The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease
    Veronica Hirsch-Reinshagen
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V4Z 5H5, Canada
    J Biol Chem 280:43243-56. 2005
    ..In addition, ABCA1 has been reported to modulate beta-amyloid (Abeta) production in vitro...
  89. pmc ATP-binding cassette transporter A1 mediates the beneficial effects of the liver X receptor agonist GW3965 on object recognition memory and amyloid burden in amyloid precursor protein/presenilin 1 mice
    James J Donkin
    Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
    J Biol Chem 285:34144-54. 2010
    ..In amyloid mouse models of AD, ABCA1 deficiency exacerbates amyloidogenesis, whereas ABCA1 overexpression ameliorates ..
  90. pmc Amyloid imaging in mild cognitive impairment subtypes
    David A Wolk
    Alzheimer s Disease Research Center, University of Pittsburgh, Pittsburgh, PA 19104, USA
    Ann Neurol 65:557-68. 2009
    We utilized the amyloid imaging ligand Pittsburgh Compound B (PiB) to determine the presence of Alzheimer's disease (AD) pathology in different mild cognitive impairment (MCI) subtypes and to relate increased PiB binding to other markers ..
  91. pmc Fibril fragmentation enhances amyloid cytotoxicity
    Wei Feng Xue
    Astbury Centre for Structural Molecular Biology, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 284:34272-82. 2009
    Fibrils associated with amyloid disease are molecular assemblies of key biological importance, yet how cells respond to the presence of amyloid remains unclear...
  92. pmc Scrambled prion domains form prions and amyloid
    Eric D Ross
    Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    Mol Cell Biol 24:7206-13. 2004
    The [URE3] prion of Saccharomyces cerevisiae is a self-propagating amyloid form of Ure2p. The amino-terminal prion domain of Ure2p is necessary and sufficient for prion formation and has a high glutamine (Q) and asparagine (N) content...
  93. ncbi Microglia, amyloid, and cognition in Alzheimer's disease: An [11C](R)PK11195-PET and [11C]PIB-PET study
    Paul Edison
    MRC Clinical Sciences Centre, Cyclotron Building Hammersmith Hospital, Imperial College London, UK
    Neurobiol Dis 32:412-9. 2008
    11C](R)PK11195-PET is a marker of activated microglia while [11C]PIB-PET detects raised amyloid load...
  94. ncbi Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice
    Radosveta Koldamova
    Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 280:43224-35. 2005
    ..To determine further the effect of ABCA1 on amyloid deposition, we used APP23 transgenic mice in which the human familial Swedish AD mutant is expressed only in ..
  95. pmc Bovine insulin filaments induced by reducing disulfide bonds show a different morphology, secondary structure, and cell toxicity from intact insulin amyloid fibrils
    Tamotsu Zako
    Bioengineering Laboratory, RIKEN Institute, Saitama, Japan
    Biophys J 96:3331-40. 2009
    b>Amyloid fibrils are associated with more than 20 diseases, including Alzheimer's disease and type II diabetes...
  96. pmc Peptides released by physiological cleavage of semen coagulum proteins form amyloids that enhance HIV infection
    Nadia R Roan
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA
    Cell Host Microbe 10:541-50. 2011
    ..Here, we report that a subset of these semenogelin fragments form amyloid fibrils that greatly enhance HIV infection...
  97. ncbi Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice
    Chad A Dickey
    Alzheimer s Disease Research Laboratory, Department of Pharmacology, University of South Florida, College of Medicine, Tampa, Florida 33612, USA
    J Neurosci 23:5219-26. 2003
    A critical question in Alzheimer's disease (AD) research is the cause of memory loss that leads to dementia. The amyloid precursor protein + presenilin-1 (APP+PS1) transgenic mouse is a model for amyloid deposition, and like AD, the mice ..
  98. pmc Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease
    K Ueda
    Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093 0624
    Proc Natl Acad Sci U S A 90:11282-6. 1993
    A neuropathological hallmark of Alzheimer disease (AD) is a widespread amyloid deposition...
  99. ncbi Disease-associated amyloid and misfolded protein aggregates activate the inflammasome
    Seth L Masters
    Immunology Research Centre, Inflammation Research Group, School of Biochemistry and Immunology, Trinity College Dublin, Ireland
    Trends Mol Med 17:276-82. 2011
    ..This review discusses the basic research behind these findings and the potential for new therapeutic interventions this affords...
  100. pmc Antimicrobial properties of amyloid peptides
    Bruce L Kagan
    Department of Psychiatry, David Geffen School of Medicine, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California 90024, USA
    Mol Pharm 9:708-17. 2012
    More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues...
  101. ncbi Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer's disease?
    Natalia N Nalivaeva
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
    J Neurochem 120:167-85. 2012
    The amyloid cascade hypothesis of Alzheimer's disease envisages that the initial elevation of amyloid β-peptide (Aβ) levels, especially of Aβ(1-42) , is the primary trigger for the neuronal cell death specific to onset of Alzheimer'..

Research Grants76

  1. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  2. Comprehensive biomarker study to capitalize on existing GWAS in 10K South Asians
    Danish Saleheen; Fiscal Year: 2010
    ..D, parathyroid hormone);and (4) inflammation and hemostasis (hsCRP, MCP-1, IL-6, sTNFRII, sVCAM-1, sICAM-1, serum amyloid A, MMP-9, E-selectin, P-selectin, CD40 ligand, fibrinogen, von Willebrand factor, and D-dimer)...
  3. Reactive (AA)Amyloidosis
    Merrill D Benson; Fiscal Year: 2013
    ..genetic, cause recurrent inflammation resulting in elevated expression of the acute phase proteins of the serum amyloid A (SAA) family. SAA, an apolipoprotein of plasma HDL, is the precursor of the amyloid fibril subunit AA...
  4. Statin modulation of immunotherapy for Alzheimer disease
    Jun Tan; Fiscal Year: 2012 the presence of extracellular senile plaques in the brain primarily composed of 40-42 amino acid length amyloid beta (A(1-40, 42) peptides...
  5. Novel PET imaging agents for early diagnosis of plaque deposition in Alzheimer's
    Padmakar Kulkarni; Fiscal Year: 2010
    ..The goal of the proposal is to develop biomarkers for the detection of amyloid plaques in living humans...
  6. Vascular dysfunction and oxidative stress in primary amyloidosis
    RAYMOND QUEZON MIGRINO; Fiscal Year: 2010
    ..It results from the deposition of misfolded amyloid proteins derived from immunoglobulin light chains and affects the heart, gut, kidneys and peripheral nerves...
  7. Alpha B crystallin as a novel therapeutic for SIRS and Sepsis
    Jonathan B Rothbard; Fiscal Year: 2011
    ..reduce in a dose dependent manner serological levels of IL-6, serum amyloid A, and C reactive protein in mice injected with LPS and (ii...
  8. Alzheimer's Disease Therapeutic
    Trevor P Castor; Fiscal Year: 2012
    ..of bryostatin 1, a potent PKC activator, dramatically enhance the generation of non-amyloidogenic soluble amyloid precursor protein (sAPP) in fibroblasts from AD patients...
  9. Drug Interactions at the Human Blood-Brain Barrier
    Jashvant D Unadkat; Fiscal Year: 2010
    ..g. beta-amyloid)...
  10. Weight Loss &Exercise Effects on Telomere Length in Postmenopausal Women
    ANNE M MCTIERNAN; Fiscal Year: 2012
    ..the trial: DNA damage repair (COMET), sex hormones, insulin &glucose, inflammation (C-reactive protein, serum amyloid A, interleukin-6), insulin like growth factor 1 and binding protein 3, and adipokines (adiponectin, leptin)...
  11. Systemic AA Amyloidosis Inhibitors
    ALAN D SNOW; Fiscal Year: 2010
    ..Systemic AA Amyloidosis is characterized by the accumulation of insoluble fibril deposits containing the AA amyloid protein in different organs throughout the body including heart, kidney, liver, spleen, lungs, skin and ..
  12. Epigenetic Analysis of iPS Cell Models of Aging and Alzheimer's Disease
    Bruce A Yankner; Fiscal Year: 2010
    ..survive under stress-related conditions associated with aging and AD, such as oxidative stress and exposure to amyloid [unreadable]-protein (A[unreadable]), and whether this changes in cells derived from AD patients...
  13. Beta Cell Adaptation to Stress in Baboon Pancreas After Partial Pancreatectomy
    FRANCO BATTISTA FOLLI; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Deposition of islet amyloid pancreatic polypeptide (IAPP) in the islets of Langerhans is the characteristic feature of human type 2 diabetic pancreas but represents the final stage of a process ..
  14. Pathogenesis of Postoperative Cognitive Dysfunction
    Zhongcong Xie; Fiscal Year: 2013
    ..unreadable]-Amyloid protein (A[unreadable]) is th key component of senile plaques in Alzheimer's disease (AD) patients, and A[..
    Gregory J Zipfel; Fiscal Year: 2013
    ..Two key observations suggest that amyloid-[unreadable] peptide (A[unreadable]) may play a role by either causing or increasing the susceptibility to ..
  16. Age-Related Decrease in A-Beta Peptide Clearance Pathways: CSF and BBB
    Conrad Earl Johanson; Fiscal Year: 2010
    ..Consequently, neuronal health and function are impaired by catabolite toxicity, e.g., beta amyloid (Ap), in the interstitial fluid (ISF) and CSF...
  17. Cellular Mechanisms for Increased Gluconeogenesis in Type 2 Diabetes
    Varman T Samuel; Fiscal Year: 2013
    ..sensitivity will be tested in two models of T2D, the ZDF rat and a transgenic rat overexpressing human islet amyloid polypeptide (HIP rat)...
  18. Autophagy and human islet amyloid polypeptide in animal models of type 2 diabetes
    Jacqueline Rivera; Fiscal Year: 2013 T2DM is accompanied by a specific islet pathology, with an approximate 60% deficit in beta cell mass and islet amyloid derived from islet amyloid polypeptide (IAPP)...
  19. Mitoenergetic Failure in Brain Aging
    Gregory J Brewer; Fiscal Year: 2013
    ..FAD ], all of which contribute to increased susceptibility to toxic stressors such as glutamate and beta-amyloid. Now we will use a well-established model of Alzheimer disease, LaFerla's 3xTg-AD mouse to test our ..
    JOHN PATTERSON ATKINSON; Fiscal Year: 2013
    ..As we age, lipids deposit in blood vessel walls (atherosclerosis), urate in joints (gout), amyloid proteins in the brain (Alzheimer's disease - AD) and lipofuscin pigments (drusen) in the retina (age-related ..
  21. Exploring Human-Induced Pluripotent Stem Cells for Alzheimer's Disease Research
    Kuo Fen Lee; Fiscal Year: 2012 applicant) Alzheimer's disease (AD) is a neurodegenerative disease characterized by the deposition of amyloid plaque in the extracellular space, formation of neurofibrillary tangles in neurons, and extensive neuronal loss...
  22. Longitudinal Study of Lipids and APOE in the Development of AD and AD Pathology
    Michelle M Mielke; Fiscal Year: 2013
    ..The roles by which ApoE influences amyloid-beta (A2) metabolism and non-A2-mediated mechanisms in AD pathogenesis, however, remain to be fully clarified...
  23. The Role of Fibrocytes in Liver Fibrosis
    Tatiana Kisseleva; Fiscal Year: 2012
    ..low numbers, our preliminary data suggest that inhibition of fibrocyte function(s) by the natural inhibitor Serum Amyloid P (SAP), results in the blockage of fibrocyte flux into fibrotic liver, and significantly attenuates liver ..
    JOHN IRWIN CLARK; Fiscal Year: 2013
    ..Synthetic peptides based on the individual interactive domains in ?B crystallin mediate the formation of amyloid fibrils and will be used to characterize the collective mechanism(s) of the interactive domains in the action of ?..
  25. Angiotensin-induced Oxidants and Vascular Cell Phenotype
    Richard Cohen; Fiscal Year: 2009
    ..cytokines, amyloid 13 peptide) and proliferative growth factors (e.g. angiotensin (Ang) II, PDGF, EGF, etc)...
  26. Regulation of HMGB1 Release in Endotoxemia
    Haichao Wang; Fiscal Year: 2013
    ..We have generated exciting preliminary data indicating that human serum amyloid A (SAA), but not SAA1, effectively induced HMGB1 release in vitro, and exacerbated endotoxin-mediated animal ..
  27. Clinical and Molecular Biology of Acute and Chronic Traumatic Encephalopathies
    JAMES WAVELL AIKEN; Fiscal Year: 2011
    ..with accumulation of aggregated proteins or protein fragments, including tau, TDP-43, the Alzheimer's amyloid precursor protein (APP), and the APP metabolite, amyloid-beta...
  28. Nanoliposome-based Treatment of Amyloid Protein (AL) Toxicity
    RAYMOND QUEZON MIGRINO; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Amyloid protein-misfolding diseases such as Alzheimer's (AD) and light chain amyloidosis (AL) remain intractable diseases with high morbidity and mortality...
  29. Anti-Aging Mitochondrial Protein Therapy for Alzheimer?s Disease and Sarcopenia
    JAMES PEPPER BENNETT; Fiscal Year: 2010
    ..In the Alzheimer's brain, there is accumulation of pathological forms of beta- amyloid and tau which suppress oxidative metabolism that eventually may cause loss of neurons...
  30. Predicting Cognitive Decline in Adults with Down Syndrome
    Ira T Lott; Fiscal Year: 2013
    ..The 2nd specific aim will assess whether amyloid uptake is increased in brain by positron emission tomography as a predictor of dementia...
  31. Environmental Determinants of Cognitive Aging in the WHI Memory Study
    Jiu Chiuan Chen; Fiscal Year: 2013
    ..Air pollution toxicopathological studies also found evidence of accelerated brain aging (e.g., 2-amyloid accumulation with or without dystrophic neuritis) in canines...
  32. Reactive Oxygen Species Signaling in the Hippocampus
    Eric Klann; Fiscal Year: 2012
    ..In one well- studied mouse model of AD, Tg2576 mice that overexpress a double mutant form of amyloid precursor protein (APP), amyloid plaque deposition was shown to be associated with oxidative damage...
  33. Serum amyloid P and chronic noncommunicable diseases
    Weibin Shi; Fiscal Year: 2010
    ..Serum amyloid P (SAP) is a prototypic member of the pentraxin family, which is involved in innate immunity and low grade ..
  34. Cognitive Complaints and Decline and B-Amyloid Deposition in Non-Demented Elderly
    BETH ELLEN SNITZ; Fiscal Year: 2013
    ..b>Amyloid-beta (A[unreadable]) imaging studies indicate that brain A[unreadable] plaques are present in 20-30% of ..
  35. Molecular Mechanisms and Treatment of Primary Amyloid AL Cardiomyopathy
    Ronglih Liao; Fiscal Year: 2013
    ..The resulting amyloid AL cardiomyopathy is unique in that it is not responsive to standard heart failure regimens and is accompanied by ..
  36. Role of serum amyloid A in interferon-gamma expression and T helper 1 cell differ
    Rong Lucy He; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Role of serum amyloid A in interferon-3 expression and T helper 1 cell differentiation Summary: The goal of this study is to determine the role of serum amyloid A (SAA) in the cell mediated adaptive ..
  37. Cell Models for Alzheimer's disease (AD): Lipids and Related Signaling Pathways
    Grace Y Sun; Fiscal Year: 2012 people with AD is associated with chronic oxidative stress and increased production of neurotoxic oligomeric amyloid beta (A?) that cause release of cytokines and other molecules that promote neurodegeneration and chronic ..
  38. The Abeta protein of Alzheimer's Disease is an antimicrobial peptide
    Robert D Moir; Fiscal Year: 2013
    ..A[unreadable] is most often characterized as an incidental catabolic byproduct of the amyloid precursor protein (APP) with no functional role...
  39. Disease-Modifying Effects of Filgastrim in a Mouse Model of AD
    Juan R Sanchez-Ramos; Fiscal Year: 2012
    ..The proposed studies are designed to elucidate the cellular and molecular mechanisms by which G-CSF reduces amyloid deposition/levels, stimulates hippocampal neurogenesis and restores synaptic functional activity in a mouse model ..
  40. Mechanism of CD40 signaling to APP metabolism
    Michael J Mullan; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is characterized by three main pathologies: amyloid deposition, tauopathy and chronic inflammation...
  41. Functional Amyloid Formation in Streptococcus mutans
    L Jeannine Brady; Fiscal Year: 2013
    ..In this proposal we show that the S. mutans cell surface-localized adhesin called P1 (Antigen I/II, PAc) is an amyloid forming protein...
  42. Pioglitazone & Exercise Effects on Older Aldults with MCI and Metabolic Syndrome
    Robert S Schwartz; Fiscal Year: 2010
    ..areas related to memory;2) IR-related changes in insulin transport into the CNS;3) effects of insulin on the amyloid cascade in the CNS;and 4) the pro-inflammatory state associated with MS...
  43. Novel Hsp90 Inhibitors to Reduce Misfolded Proteins in Alzheimer's Disease
    Mary L Michaelis; Fiscal Year: 2011
    ..Activation or up-regulation of these chaperone complexes reduces amyloid peptide (Ap) aggregates and fibrillar Tau protein in transgenic mouse models of AD neuropathology...
  44. Comparative effectiveness of Brain Imaging and Blood Biomarkers in Alzheimer??s d
    Orly Lazarov; Fiscal Year: 2010
    ..Impairments in neurogenesis are apparent very early in life, preceding amyloid deposition and memory deficits...
    Andrew J W Huang; Fiscal Year: 2011
    ..b>Amyloid fibril formation will be evaluated by Congo red and Thioflavin T assays...
  46. Role of LXR and ABCA1 in Abeta Aggregation and Toxicity
    NICHOLAS FRANCIS FITZ; Fiscal Year: 2012
    ..studies demonstrated that AD transgenic mice with engineered disruption of Abca1 have an increased level of amyloid deposition and cognitive impairments. LXR regulates the expression of Abca1 and ApoE both in humans and rodents...
    Scott J Hultgren; Fiscal Year: 2013
    ..This greatly complicates the clearance of these organisms and the ability to cure these infections. Amyloid fibers called curli are critical in the formation of a biofilm extracellular matrix by uropathogenic Escherichia ..
  48. Impact of Inflammatory Genes on Glandular Hyperplasia in Children with Sinusitis
    Mary C Rose; Fiscal Year: 2010
    ..evaluated in this study: the chemokine ligands CXCL5 and CXCL13 (not previously associated with CRS), and serum amyloid A (SAA2), serpin B4 and defensin 21 (DEFB1), which are part of the innate immune system...
  49. Immunomodulatory Roles of Amyloid-Beta and Amyloid Precursor Protein in CNS Autoi
    JACQUELINE LEIGH GRANT; Fiscal Year: 2012
    ..The goal of this proposal is to investigate how amyloid precursor protein (APP) and its metabolic derivative, amyloid-[unreadable]-42 (A[unreadable]42), regulate CNS ..
  50. Regulation and Catalysis of Human Insulin Degrading Enzyme
    Wei Jen Tang; Fiscal Year: 2013
    ..IDE) is an evolutionarily conserved, 110 kDa metalloprotease that is involved in the clearance of insulin and amyloid ? (A?)...
  51. RAGE Mediated Mechanisms of Islet Amyloid Polypeptide Cytotoxicity in Type 2 Diab
    Andisheh Abedini; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Amyloid formation plays an important role in a broad range of human diseases, including Alzheimer's disease (AD), Parkinson's disease, and type 2 diabetes (T2D)...
    Stanley B Prusiner; Fiscal Year: 2013
    ..cultured cell assays, we propose to develop additional assays for HTS that include adaptation of an amyloid seeding assay (ASA) using HuPrPSc to seed the polymerization of recombinant (rec) HuPrP as well as a humanized ..
  53. Glucose Metabolic, Amyloid, and Tau Brain Imaging in Down's Syndrome and Dementia
    GARY WILLIAM SMALL; Fiscal Year: 2013
    ..adults with Down's syndrome (DS) exhibit the neuropathological hallmarks of Alzheimer's disease (AD): amyloid senile plaques (SPs) and tau neurofibrillary tangles (NFTs)...
    Catherine E Costello; Fiscal Year: 2012
    ..The research topics include Cardiovascular Disease, Alzheimer Disease, familial and sporadic systemic amyloid diseases, prion diseases, Cancer, Huntington Disease, Lyme and Rheumatoid Arthritis, Sickle Cell Disease, ..
  55. PET and MRI Neuronal Loss and Amyloid and Tau Deposition in Alzheimer Disease
    Laurel Martin-Harris; Fiscal Year: 2012
    ..Although the hallmark physiological features- beta-amyloid plaques and tau neurofibrillary tangles- are diagnostic for the disorder, it is unknown whether the deposition of ..
  56. Effect of White Matter Disease on Gait and Balance in Cerebral Amyloid Angiopathy
    Anand Viswanathan; Fiscal Year: 2013
    Cerebral amyloid angiopathy (CAA) leads to cerebrovascular deposition of ss-amyloid resulting in vessel fragility and intracerebral hemorrhage (ICH)...
  57. Epidemiology of Biomarkers of Risk and Progression in LOAD
    Nicole Schupf; Fiscal Year: 2013
    ..measures, cardiovascular status and selected biomarkers in this elderly, multi-ethnic cohort, including lipids, amyloid peptides, sex hormones, homocysteine, insulin and C-reactive protein (CRP), and MRI...
  58. GRADS Cooperative Research Project: JHU Clinical Center
    David R Moller; Fiscal Year: 2013
    ..Proposed Aim 2 studies will explore the hypothesis that serum amyloid A, an acute phase reactant and amyloid precursor protein, is a central mediator of chronic inflammation and ..
  59. A Mouse Model for the Rare Plasma Cell Disease AL Amyloidosis
    David C Seldin; Fiscal Year: 2010
    ..that outlined the "Challenges and Opportunities for Systemic Amyloidosis Research," published in the journal Amyloid (Wright DG et al., Amyloid 14(2): 103-112, 2007). That report described animal models as "......
  60. Epigenomic impact of diet and toxicant exposure in Alzheimers disease etiology
    Iliya Lefterov; Fiscal Year: 2013
    ..detrimental effects of high fat diet (HFD) on cognitive performance and exacerbation of cerebral amyloidosis and amyloid angiopathy has been recently demonstrated in an animal model of AD...
  61. ApoE receptor pathways and abeta metabolism
    Guojun Bu; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Amyloid-[unreadable] (A[unreadable]) peptide accumulation and aggregation in the brain lead to synaptic dysfunction and neurotoxicity...
  62. Cortical Synapses and Psychosis in AD
    Robert A Sweet; Fiscal Year: 2012
    ..from cell culture, transgenic mice, and post-mortem human studies have provided converging evidence that soluble amyloid beta (A() initiates a pathophysiologic cascade leading to synapse disruption in AD...
    Kenneth Johnson; Fiscal Year: 1991
    A previously unknown putative polypeptide hormone identified as islet amyloid polypeptide (IAPP) was recently purified from islet amyloid (IA) of cats and humans with TYPE 2 diabetes mellitus (DM)...
  64. Mechanisms of Microglial Activation and Phagocytosis in*
    Gary Landreth; Fiscal Year: 2005
    Alzheimer's disease is characterized by the extensive deposition of fibrillar forms of beta-amyloid (AB) peptides into the extracellular space, and their compaction into senile plaques...
  65. Proteoglycans/Glycosaminoglycans in APP Transgenic Mice
    ALAN SNOW; Fiscal Year: 2004
    ..AD is characterized by the accumulation of insoluble fibrillar amyloid deposits containing the beta-amyloid protein (Abeta), either as extracellular amyloid plaques in the brain ..
    Peter Gorevic; Fiscal Year: 1999
    DESCRIPTION Amyloid is a generic term that encompasses a group of disorders in which extracellular hyaline material deposits in tissue that has characteristic tinctorial properties and a fibrillar structure...
    Barbara Kluve Beckerman; Fiscal Year: 2007
    ..arthritis and familial Mediterranean fever, and is characterized by extracellular fibrillar deposits of amyloid A (AA) protein, a peptide proteolytically derived from the acute phase reactant serum amyloid A (SAA)...
  68. Magnetic Resonance Imaging of Alzheimer's Amyloid Plaque
    JOSEPH PODUSLO; Fiscal Year: 2007
    ..DESCRIPTION (provided by applicant): [unreadable] This project will test the hypothesis that modifications of amyloid-beta protein (A beta) or derivatives of A beta can be used for the molecular imaging of amyloid plaques in ..
  69. Inhibitors of beta-Amyloid Production in Alzheimer's
    Gregory Hook; Fiscal Year: 2007
    ..Abnormal accumulation of extracellular brain beta-amyloid is thought to cause AD and compounds that block beta-amyloid production are predicted to be effective for ..
  70. Pathological Influence of Vasculotropic Mutant Amyloid-Beta
    William E Van Nostrand; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Cerebrovascular accumulation of the amyloid [unreadable]-protein (A[unreadable]), a condition known as cerebral amyloid angiopathy (CAA), is a common pathological feature of patients with Alzheimer&..
    Frank LaFerla; Fiscal Year: 2001
    ..The principal constituent of these plaques is a small peptide called beta-amyloid. Various histochemical and immunological reagents have been used to show that beta-amyloid deposits accumulate in ..
  72. Amyloid-Lowering Small Molecule AB-Binding Agents in AD
    William E Klunk; Fiscal Year: 2010
    ..Because of the key role of the amyloid-beta (A?) peptide in the pathophysiology of AD, A? synthesis, deposition and clearance have become important ..
  73. Loss of synapses in physiological and pathological aging
    Pascale Lacor; Fiscal Year: 2003
    ..Alzheimer's disease (AD) is a neurodegenerative disorder that is pathologically characterized by the presence of amyloid deposits composed by filaments of amyloid beta (Abeta) peptide...
  74. Untangling Amyloid Plaques With Proteases
    Jin Moo Lee; Fiscal Year: 2010
    ..A?1-42, the 42 amino-acid peptide fragment of the amyloid precursor protein (APP), has a striking propensity to aggregate into amyloid fibrils within plaques...
  75. Role of Cortical Microvascular Lesions in Amyloid-Beta Accumulation
    Chris B Schaffer; Fiscal Year: 2010
    ..In AD, amyloid-[unreadable] (A[unreadable]) peptides aggregate to form neurotoxic oligomers and eventually accumulate as amyloid ..
  76. Role of RyRs, DHPRs and Ca2+ Entry in the Inclusion Body Myositis
    Alexander Shtifman; Fiscal Year: 2010
    ..In this proposal Dr. Shtifman will investigate the effects of 2-amyloid proteins on Ca2+ dysregulation in skeletal muscle as it relates to a skeletal muscle disorder, the Inclusion Body ..