alzheimer disease

Summary

Summary: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)

Top Publications

  1. ncbi Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo
    Dominic M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 416:535-9. 2002
  2. ncbi A specific amyloid-beta protein assembly in the brain impairs memory
    Sylvain Lesne
    Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    Nature 440:352-7. 2006
  3. ncbi Tau-mediated neurodegeneration in Alzheimer's disease and related disorders
    Carlo Ballatore
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, Pennsylvania 19104 4283, USA
    Nat Rev Neurosci 8:663-72. 2007
  4. ncbi Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability
    Karie N Dahlgren
    Department of Medicine, Evanston Northwestern Healthcare Research Institute, Evanston, Illinois 60201, USA
    J Biol Chem 277:32046-53. 2002
  5. ncbi Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain
    Bruce Fischl
    Massachusetts General Hospital, Nuclear Magnetic Resonance Center, Rm 2328, Building 149, 13th Street, Charlestown, MA 02129, USA
    Neuron 33:341-55. 2002
  6. ncbi The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics
    John Hardy
    Laboratories of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Science 297:353-6. 2002
  7. ncbi An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest
    Rahul S Desikan
    Department of Anatomy and Neurobiology, Boston University School of Medicine, 715 Albany Street, W701, Boston, MA 02118, USA
    Neuroimage 31:968-80. 2006
  8. pmc ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models
    Paige E Cramer
    Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Science 335:1503-6. 2012
  9. 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
  10. pmc Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
    Reisa A Sperling
    Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Alzheimers Dement 7:280-92. 2011

Detail Information

Publications340 found, 100 shown here

  1. ncbi Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo
    Dominic M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 416:535-9. 2002
    ....
  2. ncbi A specific amyloid-beta protein assembly in the brain impairs memory
    Sylvain Lesne
    Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    Nature 440:352-7. 2006
    ..We propose that Abeta*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease...
  3. ncbi Tau-mediated neurodegeneration in Alzheimer's disease and related disorders
    Carlo Ballatore
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, Pennsylvania 19104 4283, USA
    Nat Rev Neurosci 8:663-72. 2007
    ....
  4. ncbi Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability
    Karie N Dahlgren
    Department of Medicine, Evanston Northwestern Healthcare Research Institute, Evanston, Illinois 60201, USA
    J Biol Chem 277:32046-53. 2002
    ....
  5. ncbi Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain
    Bruce Fischl
    Massachusetts General Hospital, Nuclear Magnetic Resonance Center, Rm 2328, Building 149, 13th Street, Charlestown, MA 02129, USA
    Neuron 33:341-55. 2002
    ..The technique is shown to be comparable in accuracy to manual labeling, and of sufficient sensitivity to robustly detect changes in the volume of noncortical structures that presage the onset of probable Alzheimer's disease...
  6. ncbi The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics
    John Hardy
    Laboratories of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Science 297:353-6. 2002
    ..The rest of the disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between Abeta production and Abeta clearance...
  7. ncbi An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest
    Rahul S Desikan
    Department of Anatomy and Neurobiology, Boston University School of Medicine, 715 Albany Street, W701, Boston, MA 02118, USA
    Neuroimage 31:968-80. 2006
    ....
  8. pmc ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models
    Paige E Cramer
    Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Science 335:1503-6. 2012
    ..Thus, RXR activation stimulates physiological Aβ clearance mechanisms, resulting in the rapid reversal of a broad range of Aβ-induced deficits...
  9. 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
    ..These results indicate that different types of soluble amyloid oligomers have a common structure and suggest they share a common mechanism of toxicity...
  10. pmc Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
    Reisa A Sperling
    Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Alzheimers Dement 7:280-92. 2011
    ....
  11. pmc The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
    Guy M McKhann
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Alzheimers Dement 7:263-9. 2011
    ..Much work lies ahead for validating the biomarker diagnosis of AD dementia...
  12. 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 relationship was most robust in the parietal cortex (r = -0.72; p = 0.0001). The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects...
  13. pmc Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations
    Ju Hyun Lee
    Center for Dementia Research, Nathan S Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Cell 141:1146-58. 2010
    ..Defective lysosomal proteolysis represents a basis for pathogenic protein accumulations and neuronal cell death in AD and suggests previously unidentified therapeutic targets...
  14. ncbi Alzheimer's disease
    Kaj Blennow
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren s University Hospital, Molndal, Sweden
    Lancet 368:387-403. 2006
    ..This seminar reviews the key aspects of the disease, including epidemiology, genetics, pathogenesis, diagnosis, and treatment, as well as recent developments and controversies...
  15. pmc Pathways towards and away from Alzheimer's disease
    Mark P Mattson
    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA
    Nature 430:631-9. 2004
    ..But rapid progress towards understanding the cellular and molecular alterations that are responsible for the neuron's demise may soon help in developing effective preventative and therapeutic strategies...
  16. ncbi Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
    E H Corder
    Department of Medicine, Joseph and Kathleen Bryan Alzheimer s Disease Research Center, Duke University Medical Center, Durham, NC 27710
    Science 261:921-3. 1993
    ..Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80...
  17. ncbi Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE
    R Vassar
    Amgen, Inc, One Amgen Center Drive, M S 29 2 B, Thousand Oaks, CA 91320 1799, USA
    Science 286:735-41. 1999
    ..Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease...
  18. pmc Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders
    Berislav V Zlokovic
    Department of Physiology and Biophysics, and Center for Neurodegeneration and Regeneration at the Zilkha Neurogenetic Institute, University of Southern California, Keck School of Medicine, 1501 San Pablo Street, Los Angeles, California 90089, USA
    Nat Rev Neurosci 12:723-38. 2011
    ..This article examines mechanisms of BBB dysfunction in neurodegenerative disorders, notably Alzheimer's disease, and highlights therapeutic opportunities relating to these neurovascular deficits...
  19. ncbi Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria
    Bruno Dubois
    INSERM U610, Hopital de la Salpetriere, Paris, France
    Lancet Neurol 6:734-46. 2007
    ..Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specificity, and accuracy...
  20. pmc TREM2 variants in Alzheimer's disease
    Rita Guerreiro
    University College London UCL Institute of Neurology, London, United Kingdom
    N Engl J Med 368:117-27. 2013
    ..Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia...
  21. pmc Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease
    Randy L Buckner
    Department of Psychology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA
    J Neurosci 29:1860-73. 2009
    ....
  22. ncbi Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
    A Goate
    Department of Biochemistry, St Mary s Hospital Medical School, London, UK
    Nature 349:704-6. 1991
    ..Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene...
  23. doi A mutation in APP protects against Alzheimer's disease and age-related cognitive decline
    Thorlakur Jonsson
    deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
    Nature 488:96-9. 2012
    ..Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms...
  24. 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...
  25. ncbi A beta oligomers - a decade of discovery
    Dominic M Walsh
    Laboratory for Neurodegenerative Research, The Conway Institute, University College Dublin, Belfield, Dublin, Republic of Ireland
    J Neurochem 101:1172-84. 2007
    ..Here we review recent progress in understanding the role of soluble oligomers in Alzheimer's disease...
  26. pmc Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers
    Juha Lauren
    Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Nature 457:1128-32. 2009
    ..Thus, PrP(C) is a mediator of amyloid-beta-oligomer-induced synaptic dysfunction, and PrP(C)-specific pharmaceuticals may have therapeutic potential for Alzheimer's disease...
  27. pmc Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders
    Mathias Jucker
    Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany
    Ann Neurol 70:532-40. 2011
    ..In Alzheimer disease (the most prevalent cerebral proteopathy), the two principal aggregating proteins are β-amyloid (Aβ) and ..
  28. doi The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes
    Iryna Benilova
    Center for Human Genetics and Leuven Institute for Neurodegenerative diseases LIND, University of Leuven, Leuven, Belgium
    Nat Neurosci 15:349-57. 2012
    ..Here we critically review the evidence supporting toxic Aβ oligomers as drivers of neurodegeneration and make some suggestions that might facilitate progress in this complex field...
  29. pmc Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks
    Jorge J Palop
    Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, California, USA
    Nat Neurosci 13:812-8. 2010
    ..Strategies that block these Abeta effects may prevent cognitive decline in Alzheimer's disease. Potential obstacles and next steps toward this goal are discussed...
  30. pmc Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease
    Paul Hollingworth
    Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK
    Nat Genet 43:429-35. 2011
    ..0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10))...
  31. ncbi Mild cognitive impairment as a diagnostic entity
    R C Petersen
    Department of Neurology, Alzheimer s Disease Research Center, Mayo Clinic College of Medicine, Rochester, MN, USA
    J Intern Med 256:183-94. 2004
    ..By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations...
  32. pmc The role of apolipoprotein E in Alzheimer's disease
    Jungsu Kim
    Department of Neurology, Developmental Biology, Hope Center for Neurological Disorders, Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 63:287-303. 2009
    ..Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE...
  33. ncbi Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model
    Erik D Roberson
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Science 316:750-4. 2007
    ..Thus, tau reduction can block Abeta- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer's disease and related conditions...
  34. ncbi Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases
    Monica Bucciantini
    Dipartimento di Scienze Biochimiche, Viale Morgagni 50, Universita degli Studi di Firenze, 50134 Firenze, Italy
    Nature 416:507-11. 2002
    ..This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases...
  35. pmc Decreased clearance of CNS beta-amyloid in Alzheimer's disease
    Kwasi G Mawuenyega
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 330:1774. 2010
    ..On average, there were no differences in Aβ40 or Aβ42 production rates. Thus, the common late-onset form of Alzheimer's disease is characterized by an overall impairment in Aβ clearance...
  36. pmc APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
    Anatoly Nikolaev
    Division of Research, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 457:981-9. 2009
    ..Our results indicate that APP and DR6 are components of a neuronal self-destruction pathway, and suggest that an extracellular fragment of APP, acting via DR6 and caspase 6, contributes to Alzheimer's disease...
  37. doi Alzheimer's disease
    Clive Ballard
    Wolfson Centre for Age Related Diseases, King s College London, London, UK
    Lancet 377:1019-31. 2011
    ..In this Seminar, we provide an overview of recent evidence regarding the epidemiology, pathogenesis, diagnosis, and treatment of Alzheimer's disease, and discuss potential ways to reduce the risk of developing the disease...
  38. pmc Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression
    Sébastien S Hébert
    Center for Human Genetics, Katholieke Universiteit Leuven and Department of Molecular and Developmental Genetics, VIB, Herestraat 49 bus 602, B 3000 Leuven, Belgium
    Proc Natl Acad Sci U S A 105:6415-20. 2008
    ..We propose that loss of specific miRNAs can contribute to increased BACE1 and Abeta levels in sporadic AD...
  39. pmc Variant of TREM2 associated with the risk of Alzheimer's disease
    Thorlakur Jonsson
    deCODE Genetics, Reykjavik, Iceland
    N Engl J Med 368:107-16. 2013
    ..Few rare variants affecting the risk of late-onset Alzheimer's disease have been found...
  40. pmc Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease
    Adam C Naj
    The John P Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA
    Nat Genet 43:436-41. 2011
    The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3)...
  41. ncbi Intracellular amyloid-beta in Alzheimer's disease
    Frank M LaFerla
    Department of Neurobiology and Behaviour, and Institute for Brain Aging and Dementia, University of California, Irvine, California 92697 4545, USA
    Nat Rev Neurosci 8:499-509. 2007
    ....
  42. ncbi Small-world networks and functional connectivity in Alzheimer's disease
    C J Stam
    Department of Clinical Neurophysiology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
    Cereb Cortex 17:92-9. 2007
    ..Graph theoretical analysis may be a useful approach to study the complexity of patterns of interrelations between EEG channels...
  43. doi DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease
    Gwenaelle Douaud
    FMRIB Centre, University of Oxford, UK
    Neuroimage 55:880-90. 2011
    ....
  44. pmc Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease
    Barry Boland
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 28:6926-37. 2008
    ..Therapeutic modulation of autophagy in AD may, therefore, require targeting late steps in the autophagic pathway...
  45. ncbi Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
    R Sherrington
    Department of Medicine Neurology, University of Toronto, Ontario, Canada
    Nature 375:754-60. 1995
    ..Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3...
  46. ncbi Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective
    Rudolph E Tanzi
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Massachussetts General Hospital, Harvard Medical School, Charlestown, Massachussetts 02129, USA
    Cell 120:545-55. 2005
    ..Here we assess the amyloid hypothesis based on both known and putative Alzheimer's disease genes...
  47. ncbi RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease
    S D Yan
    Department of Pathology, Columbia University, College of Physicians and Surgeons, New York 10032, USA
    Nature 382:685-91. 1996
    ..Increased expressing of RAGE in Alzheimer's disease brain indicates that it is relevant to the pathogenesis of neuronal dysfunction and death...
  48. pmc Probing the biology of Alzheimer's disease in mice
    Karen H Ashe
    N Bud Grossman Center for Memory Research and Care, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    Neuron 66:631-45. 2010
    ....
  49. ncbi Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium
    L A Farrer
    Department of Neurology, Boston University School of Medicine, Mass 02118, USA
    JAMA 278:1349-56. 1997
    To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations.
  50. pmc Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
    Leslie M Shaw
    Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Ann Neurol 65:403-13. 2009
    ..Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects...
  51. pmc The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
    Marilyn S Albert
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Alzheimers Dement 7:270-9. 2011
    ..Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings...
  52. pmc Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice
    Suzanne E Hickman
    Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, and Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129
    J Neurosci 28:8354-60. 2008
    ..Antiinflammatory therapy for AD should take this dichotomous microglial role into consideration...
  53. ncbi Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease
    Alain R Simard
    Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, 2705 Laurier Boul, Quebec G1V 4G2, Canada
    Neuron 49:489-502. 2006
    ..Therapeutic strategies aiming to improve their recruitment could potentially lead to a new powerful tool for the elimination of toxic senile plaques...
  54. pmc Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
    Clifford R Jack
    Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA jack cliff
    Lancet Neurol 9:119-28. 2010
    ....
  55. doi Graph theoretical analysis of magnetoencephalographic functional connectivity in Alzheimer's disease
    C J Stam
    Department of Clinical Neurophysiology and MEG, Amsterdam, The Netherlands
    Brain 132:213-24. 2009
    ..The modelling results suggest that highly connected neural network 'hubs' may be especially at risk in Alzheimer's disease...
  56. 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
    ..These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment...
  57. doi Structural insights into aberrant topological patterns of large-scale cortical networks in Alzheimer's disease
    Yong He
    McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4
    J Neurosci 28:4756-66. 2008
    ..This work has implications for our understanding of how functional deficits in patients are associated with their underlying structural (morphological) basis...
  58. pmc Neuropathological alterations in Alzheimer disease
    Alberto Serrano-Pozo
    Alzheimer Research Unit of the MassGeneral Institute for Neurodegenerative Disease, Department of Neurology of the Massachusetts General Hospital, and Harvard Medical School, Charlestown, Massachusetts, USA, 02129 4404
    Cold Spring Harb Perspect Med 1:a006189. 2011
    The neuropathological hallmarks of Alzheimer disease (AD) include "positive" lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and "negative" lesions such as neuronal and ..
  59. pmc Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways
    Jeremy A Miller
    Interdepartmental Program for Neuroscience, Department of Human Genetics and Biostatistics, University of California, Los Angeles, CA 90095 1769, USA
    Proc Natl Acad Sci U S A 107:12698-703. 2010
    ..We also identify several robust human-specific modules, including one strongly correlated with measures of Alzheimer disease progression across multiple data sets, whose hubs are poorly-characterized genes likely involved in ..
  60. pmc NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice
    Michael T Heneka
    Clinical Neuroscience Unit, Department of Neurology, University of Bonn, Sigmund Freud Strasse 25, 53127 Bonn, Germany
    Nature 493:674-8. 2013
    ..These results show an important role for the NLRP3/caspase-1 axis in the pathogenesis of Alzheimer's disease, and suggest that NLRP3 inflammasome inhibition represents a new therapeutic intervention for the disease...
  61. pmc Clinical and biomarker changes in dominantly inherited Alzheimer's disease
    Randall J Bateman
    Washington University School of Medicine, Department of Neurology, 660 S Euclid Ave, Box 8111, St Louis, MO 63110, USA
    N Engl J Med 367:795-804. 2012
    ..Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease...
  62. doi Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial
    Nicola T Lautenschlager
    WA Centre for Health and Ageing, University of Western Australia, Melbourne, Australia
    JAMA 300:1027-37. 2008
    ..Many observational studies have shown that physical activity reduces the risk of cognitive decline; however, evidence from randomized trials is lacking...
  63. ncbi Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study
    Kun Wang
    National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, People s Republic of China
    Hum Brain Mapp 28:967-78. 2007
    ..In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks...
  64. ncbi Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression
    Maria Manczak
    Neurogenetics Laboratory, Neurological Sciences Institute, Oregon Health and Science University, 505 NW 185th Aveue, Beaverton, 97006, USA
    Hum Mol Genet 15:1437-49. 2006
    ..These findings suggest that early mitochondrially targeted therapeutic interventions may be effective in delaying AD progression in elderly individuals and in treating AD patients...
  65. ncbi Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo
    Fusheng Yang
    Department of Medicine, UCLA, Los Angeles, CA 90095, USA
    J Biol Chem 280:5892-901. 2005
    ..These data suggest that low dose curcumin effectively disaggregates Abeta as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD...
  66. pmc Impaired balance of mitochondrial fission and fusion in Alzheimer's disease
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Neurosci 29:9090-103. 2009
    ..Based on these findings, we suggest that an altered balance in mitochondrial fission and fusion is likely an important mechanism leading to mitochondrial and neuronal dysfunction in AD brain...
  67. doi Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models
    Lars M Ittner
    Alzheimer s and Parkinson s Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Sydney NSW 2050, Australia
    Cell 142:387-97. 2010
    ..Our findings suggest that this dendritic role of tau confers Abeta toxicity at the postsynapse with direct implications for pathogenesis and treatment of AD...
  68. pmc Genome-wide analysis of genetic loci associated with Alzheimer disease
    Sudha Seshadri
    Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA
    JAMA 303:1832-40. 2010
    Genome-wide association studies (GWAS) have recently identified CLU, PICALM, and CR1 as novel genes for late-onset Alzheimer disease (AD).
  69. pmc The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI methods
    Clifford R Jack
    Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Magn Reson Imaging 27:685-91. 2008
    ..The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom-based monitoring of all scanners could be used as a model for other multisite trials...
  70. pmc Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells
    Mason A Israel
    Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA
    Nature 482:216-20. 2012
    ..More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients...
  71. pmc Automatic classification of MR scans in Alzheimer's disease
    Stefan Kloppel
    Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK
    Brain 131:681-9. 2008
    ..Thirdly, the method is robust and can be generalized across different centres. This suggests an important role for computer based diagnostic image analysis for clinical practice...
  72. ncbi Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation
    Holly Oakley
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 26:10129-40. 2006
    ..Thus, 5XFAD mice rapidly recapitulate major features of AD amyloid pathology and may be useful models of intraneuronal Abeta42-induced neurodegeneration and amyloid plaque formation...
  73. pmc Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
    Denise Harold
    Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK
    Nat Genet 41:1088-93. 2009
    ..5 x 10(-10), odds ratio = 0.86; rs3851179, P = 1.3 x 10(-9), odds ratio = 0.86)...
  74. pmc Alzheimer mechanisms and therapeutic strategies
    Yadong Huang
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Cell 148:1204-22. 2012
    ..However, investigative and drug development efforts should be diversified to fully address the multifactoriality of the disease...
  75. pmc Propagation of tau pathology in a model of early Alzheimer's disease
    Alix de Calignon
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Neuron 73:685-97. 2012
    ..These data suggest that a sequence of progressive misfolding of tau proteins, circuit-based transfer to new cell populations, and deafferentation induced degeneration are part of a process of tau-induced neurodegeneration...
  76. pmc Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory
    Ganesh M Shankar
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nat Med 14:837-42. 2008
    ..We conclude that soluble Abeta oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species...
  77. ncbi What is cognitive reserve? Theory and research application of the reserve concept
    Yaakov Stern
    G H Sergievsky Center, The Taub Institute, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    J Int Neuropsychol Soc 8:448-60. 2002
    ..Epidemiologic and imaging data that help to develop and support the concept of reserve are presented...
  78. pmc Trafficking and proteolytic processing of APP
    Christian Haass
    DZNE German Center for Neurodegenerative Diseases, 80336 Munich, Germany Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    Cold Spring Harb Perspect Med 2:a006270. 2012
    Accumulations of insoluble deposits of amyloid β-peptide are major pathological hallmarks of Alzheimer disease. Amyloid β-peptide is derived by sequential proteolytic processing from a large type I trans-membrane protein, the β-..
  79. pmc Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration
    Ming Jin
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:5819-24. 2011
    b>Alzheimer disease is a major cause of cognitive failure, and a pathogenically related but more subtle process accounts for many cases of mild memory symptoms in older humans...
  80. ncbi Regional coherence changes in the early stages of Alzheimer's disease: a combined structural and resting-state functional MRI study
    Yong He
    National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100080, PR China
    Neuroimage 35:488-500. 2007
    ..Finally, our study indicated that regional brain atrophy could be an important consideration in functional imaging studies of neurodegenerative diseases...
  81. pmc The projected effect of risk factor reduction on Alzheimer's disease prevalence
    Deborah E Barnes
    Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94121, USA
    Lancet Neurol 10:819-28. 2011
    ..A 10-25% reduction in all seven risk factors could potentially prevent as many as 1·1-3·0 million AD cases worldwide and 184,000-492,000 cases in the USA...
  82. ncbi Alzheimer's disease is a synaptic failure
    Dennis J Selkoe
    Center for Neurologic Diseases, Brigham and Women s Hospital, and the Harvard Center for Neurodegeneration and Repair, Boston, MA 02115, USA
    Science 298:789-91. 2002
    ....
  83. pmc Global prevalence of dementia: a Delphi consensus study
    Cleusa P Ferri
    Section of Epidemiology, Institute of Psychiatry, King s College, London, UK
    Lancet 366:2112-7. 2005
    ..100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region...
  84. pmc Neurotoxicity of amyloid β-protein: synaptic and network dysfunction
    Lennart Mucke
    Gladstone Institute of Neurological Disease and University of California, San Francisco, San Francisco, California, USA
    Cold Spring Harb Perspect Med 2:a006338. 2012
    ..Modern analyses of this problem utilize electrophysiology coupled with synaptic biochemistry and behavioral phenotyping of animal models to elucidate the affected circuits and assess the effects of potential therapeutic interventions...
  85. ncbi Phases of A beta-deposition in the human brain and its relevance for the development of AD
    Dietmar R Thal
    Department of Anatomy, J W Goethe University, Frankfurt am Main, Germany
    Neurology 58:1791-800. 2002
    ..The deposition of the amyloid beta protein (Abeta) is a histopathologic hallmark of AD. The regions of the medial temporal lobe (MTL) are hierarchically involved in Abeta-deposition...
  86. pmc Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI
    Michael D Greicius
    Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305 5719, USA
    Proc Natl Acad Sci U S A 101:4637-42. 2004
    ..Finally, a goodness-of-fit analysis applied at the individual subject level suggests that activity in the default-mode network may ultimately prove a sensitive and specific biomarker for incipient AD...
  87. doi Amyloid-β and tau--a toxic pas de deux in Alzheimer's disease
    Lars M Ittner
    Alzheimer s and Parkinson s Disease Laboratory, Brain and Mind Research Institute, The University of Sydney, Camperdown, 100 Mallett Street, NSW 2050, Australia
    Nat Rev Neurosci 12:65-72. 2011
    ..As we gain a deeper understanding of the different cellular functions of tau, the focus shifts from the axon, where tau has a principal role as a microtubule-associated protein, to the dendrite, where it mediates amyloid-β toxicity...
  88. ncbi Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease
    Jorge J Palop
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 55:697-711. 2007
    ..Aberrant increases in network excitability and compensatory inhibitory mechanisms in the hippocampus may contribute to Abeta-induced neurological deficits in hAPP mice and, possibly, also in humans with AD...
  89. doi The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics
    Eric Karran
    Janssen Research and Development, Neuroscience Therapeutic Area, Turnhoutseweg 30, 2340 Beerse, Belgium com
    Nat Rev Drug Discov 10:698-712. 2011
    ....
  90. doi Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis
    George S Bloom
    Departments of Biology and Cell Biology, University of Virginia, Charlottesville
    JAMA Neurol 71:505-8. 2014
    The defining features of Alzheimer disease (AD) include conspicuous changes in both brain histology and behavior...
  91. pmc Replication of CLU, CR1, and PICALM associations with alzheimer disease
    Minerva M Carrasquillo
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd, Birdsall Building, Jacksonville, FL 32224, USA
    Arch Neurol 67:961-4. 2010
    To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease.
  92. doi The genetics of Alzheimer disease: back to the future
    Lars Bertram
    Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
    Neuron 68:270-81. 2010
    Three decades of genetic research in Alzheimer disease (AD) have substantially broadened our understanding of the pathogenetic mechanisms leading to neurodegeneration and dementia...
  93. ncbi Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction
    Salvatore Oddo
    Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA
    Neuron 39:409-21. 2003
    ....
  94. doi CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment
    Niklas Mattsson
    Institute of Neuroscience and Physiology, Department of Neurochemistry and Psychiatry, the Sahlgrenska Academy at University of Gothenburg, Molndal, Sweden
    JAMA 302:385-93. 2009
    ..studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been ..
  95. pmc GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers
    Eric M Reiman
    Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
    Neuron 54:713-20. 2007
    ..Our findings suggest that GAB2 modifies LOAD risk in APOE epsilon4 carriers and influences Alzheimer's neuropathology...
  96. doi miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model
    Soon Tae Lee
    Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea
    Ann Neurol 72:269-77. 2012
    b>Alzheimer disease (AD) brains are deficient in brain-derived neurotrophic factor (BDNF), which regulates synaptic plasticity and memory...
  97. pmc GSK-3: tricks of the trade for a multi-tasking kinase
    Bradley W Doble
    Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
    J Cell Sci 116:1175-86. 2003
    ..Although they are just starting to be characterized in cell culture experiments, these new inhibitors hold promise as therapeutic agents...
  98. doi Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease
    Marcello D'Amelio
    Dulbecco Telethon Institute at the Laboratory of Molecular Neuroembryology, Istituto di Ricerca e Cura a Carattere Scientifico IRCCS Fondazione Santa Lucia, Rome, Italy
    Nat Neurosci 14:69-76. 2011
    ..These findings indicate that caspase-3 is a potential target for pharmacological therapy during early disease stages...
  99. pmc Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
    Chia Chen Liu
    Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China
    Nat Rev Neurol 9:106-18. 2013
    ..APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the ε4 allele are at increased risk of AD compared with those carrying the ..
  100. doi Revising the definition of Alzheimer's disease: a new lexicon
    Bruno Dubois
    Pierre and Marie Curie University, Research Centre of the Institute of the Brain and Spinal Cord, UMR, AP HP, Pitié Salpêtrière Hospital Group, Paris, France
    Lancet Neurol 9:1118-27. 2010
    ..The cornerstone of this lexicon is to consider AD solely as a clinical and symptomatic entity that encompasses both predementia and dementia phases...
  101. pmc Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease
    Sudad Saman
    Department of Biological Sciences, University of Massachusetts, Lowell, Massachusetts 01854, USA
    J Biol Chem 287:3842-9. 2012
    ..in human CSF samples and is phosphorylated at Thr-181 (AT270), an established phosphotau biomarker for Alzheimer disease (AD), in both M1C cells and in CSF samples from patients with mild (Braak stage 3) AD...

Research Grants72

  1. Reactive (AA)Amyloidosis
    Merrill D Benson; Fiscal Year: 2013
    ..also has an increase in prevalence of the age related amyloidoses including immunoglobulin amyloid, Alzheimer disease and senile cardiac amyloidosis...
  2. Statin modulation of immunotherapy for Alzheimer disease
    Jun Tan; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Statin modulation of immunotherapy for Alzheimer disease Summary/Abstract Alzheimer's disease (AD) is the most common dementing illness in the elderly and becoming major veteran's health ..
  3. Role of MicroRNA mi R-33 in Controlling Cholesterol/Lipid Homeostasis
    Anders M Naar; Fiscal Year: 2010
    ..These studies should provide novel therapeutic strategies aimed at increasing HDL synthesis and cholesterol clearance in patients with cardiovascular disease. ..
  4. Beta Cell Adaptation to Stress in Baboon Pancreas After Partial Pancreatectomy
    FRANCO BATTISTA FOLLI; Fiscal Year: 2010
    ..Toxic IAPP fibrils and oligomers share a common structure with Alzheimer Disease (AD)-related [unreadable]-amyloid (A[unreadable]) fibrils and oligomers, suggesting a similar pathogenesis ..
  5. OLFACTORY RECEPTOR COPY NUMBER ASSOCIATION WITH AGE AT ONSET OF ALZHEIMER DISEASE
    Kinga Szigeti; Fiscal Year: 2013
    ..These specific genetic markers are attractive risk factor candidates because gene dosage can be modified by small molecules (medications) thus may translate to therapy that delays disease onset. ..
  6. Combined neuroprotection and metabolic correction to treat leukodystrophies
    ERNESTO ROQUE BONGARZONE; Fiscal Year: 2013
    ..to permanent neurological deficits in several neurodegenerative disorders, including multiple sclerosis, Alzheimer disease, Parkinson disease and others...
  7. Microvascular Dysfunction in Hyperhomocysteinemia
    Shawn E Bearden; Fiscal Year: 2012
    ..dysfunction caused by HHcy, a risk factor for cardiovascular disease, venous thromboembolism, stroke, and Alzheimer disease. PUBLIC HEALTH RELEVANCE: The lining of the microvasculature, the endothelium, communicates nutrient needs ..
  8. International Conf on Alzheimer Disease and Related Disorders in the Middle East
    Changiz Geula; Fiscal Year: 2013
    ..The organizers have successfully convened five editions of this conference in the past, and based on past experience expect an even more successful sixth conference. ..
  9. Mitoenergetic Failure in Brain Aging
    Gregory J Brewer; Fiscal Year: 2013
    ..Now we will use a well-established model of Alzheimer disease, LaFerla's 3xTg-AD mouse to test our hypothesis that redox potential and mitoenergetic function are ..
  10. Mutational Cloning in Familial Dementia and Alzheimers Disease
    Wendy H Raskind; Fiscal Year: 2010
    ..We will employ newly available powerful sequencing and bioinformatics techniques to detect causative mutations in families with apparent autosomal dominant dementia where the available affected persons are too few for linkage analyses. ..
  11. Generating Blood-based Diagnosis for Alzheimer Disease
    Eugenia Wang; Fiscal Year: 2012
    ..being the first such AD diagnostic, indicating not only disease presence, but also its progress (and even drug efficacy monitoring), a huge strate- gic gain for the victims of this costly disease, and our society at large! ..
  12. Neurotrophic Factors: Genetic Variation and Serum Levels in Brain Aging
    Sudha Seshadri; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Alzheimer disease (AD) imposes a substantial societal burden. Clinical AD likely results through the interaction of 3 factors: reserve, AD- and vascular pathology...
  13. C3, CR1, CRRY: INTERACTIONS, HOMEOSTASIS AND TRANSLATIONAL IMPLICATIONS
    JOHN PATTERSON ATKINSON; Fiscal Year: 2013
    ..It is involved in many common human diseases featuring deposition of altered proteins in the brain (Alzheimer Disease), lipids in vessel walls (heart attacks and strokes) and pigments in the retina (age-related macular ..
  14. Glucocerebrosidase mutations in a mouse synucleinopathy model
    Robert L Nussbaum; Fiscal Year: 2011
    ..accounts for ~10% of cases of all dementia, although some estimates suggest it is nearly as frequent as Alzheimer disease (AD) as a cause of dementia in the elderly...
  15. Rescuing Niemann-Pick C Disease: Pathways of Liver and Brain Degeneration
    Matthew P Scott; Fiscal Year: 2013
    ..Some, including NPC, have similarities to Alzheimer disease. We have used a novel approach to engineer mice that will allow us to learn how different cell types and ..
  16. Predicting Cognitive Decline in Adults with Down Syndrome
    Ira T Lott; Fiscal Year: 2013
    ..syndrome and to ultimately provide a platform for early intervention to prevent the dementia associated with Alzheimer disease. Individuals with Down syndrome have an increased incidence of Alzheimer disease over age 40 years...
  17. Translating Dosage Compensation to Trisomy
    Jeanne Bentley Lawrence; Fiscal Year: 2010
    ..altered facial structure and numerous other health issues, including greatly increased incidence of early Alzheimer Disease cardiac defects, and hematological defects and early childhood leukemia...
  18. Employing Familial AD Induced Pluripotent Stem Cells to Study Neurodegeneration
    Suman Jayadev; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The rising global prevalence of Alzheimer disease (AD) has heightened the urgency to develop effective AD therapeutics...
  19. Transgenic Study of ALS-Linked CCS Mutations
    Han Xiang Deng; Fiscal Year: 2011
    ..genes produce similar disease phenotypes, such as mutations in the homologous genes presenilin 1 and 2 cause Alzheimer disease. Because the copper chaperone for SOD1 (CCS) shares high homology with SOD1 and overexpression of wild-type ..
  20. Age-related Response of Hippocampal Neurons to Stress
    Gregory Brewer; Fiscal Year: 2009
    ..causes people with congenital mutations in APP or presenilin to wait decades before invariably developing Alzheimer disease (AD) with cognitive deficits and brain pathology? Our previous NIA grant began to investigate the aging ..
  21. MALDI-TOF/TOF MS TO SUPPORT BIOMEDICAL RESEARCH
    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 ..
  22. PET and MRI Neuronal Loss and Amyloid and Tau Deposition in Alzheimer Disease
    Laurel Martin-Harris; Fiscal Year: 2012
    ..At the same time this investigation will contribute to our knowledge of the effects of healthy aging on human learning and memory. ..
  23. Physiological mechanisms responsible for cognitive impairments in Dravet Syndrome
    Pierre Pascal Lenck-Santini; Fiscal Year: 2013
    ..1 are observed in various models of Alzheimer disease (AD). Nav1...
  24. Structure and Function of Endothelial Fenestrae
    RADU VIRGIL STAN; Fiscal Year: 2010
    ..chronic inflammation (both viral and bacterial infections, transplant rejection, allergic encephalomyelytis, Alzheimer disease), atherosclerosis, preeclampsia, toxic liver injury and cirrhosis where modulations of endothelial fenestrae ..
  25. Cortical Synapses and Psychosis in AD
    Robert A Sweet; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Psychosis occurs in 40-60% of subjects with Alzheimer disease (Alzheimer disease + Psychosis, AD+P)...
  26. Epigenomic impact of diet and toxicant exposure in Alzheimers disease etiology
    Iliya Lefterov; Fiscal Year: 2013
    ....
  27. From Defective Microglia to Cortical Activity and Pathological Behavior
    Mario R Capecchi; Fiscal Year: 2013
    ..including obsessive compulsive disorder (OCD), major depression, bipolar disorder, autism, schizophrenia and Alzheimer disease. In addition, results from genome wide association studies suggest that genes whose dysfunction have been ..
  28. Preclinical Alzheimers Disease Drug Development of Novel MAPK Inhibitors
    DANIEL MARTIN WATTERSON; Fiscal Year: 2013
    ..falls well within this timeline and offers the potential for new molecular entity (NME) entry into the multi-drug arsenal needed to delay onset, slow progression, and treat existing AD across the long timeline of disease progression ..
  29. Role of Presenilin in Idiopathic Dilated Cardiomyopathy
    Federica Del Monte; Fiscal Year: 2013
    ..and disease development remains inconclusive also for the known diseases of protein misfolding such as Alzheimer Disease. Similarly to cases of early onset familial Alzheimer Disease, mutations in the PSEN1 and 2 genes have been ..
  30. Functional Analysis of ACAT
    Ta Yuan Chang; Fiscal Year: 2013
    ..ACAT1 is a potential target for treating Alzheimer disease and other diseases in humans...
  31. Use of a Fragile X premutation knock-in mouse to study FXPOI
    Joshua Johnson; Fiscal Year: 2013
    ..PM carriers not only have increased fertility problems, but are at greater risk of cardiovascular disease, Alzheimer disease, osteoporosis and other problems that are seen at higher frequency in menopausal women...
  32. Role of cofilin pathology in mouse models of cognitive impairment
    James R Bamburg; Fiscal Year: 2013
    ..dephosphorylation (activation) and oxidation to dimers when neurons are stressed by agents associated with Alzheimer disease (AD), all of which increase reactive oxygen species (ROS)...
  33. Micro RNA-146a (miRNA-146a) signaling in Alzheimers disease (AD)
    Walter J Lukiw; Fiscal Year: 2013
    ....
  34. Presenilin 2 and Neuroinflammation
    Suman Jayadev; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Alzheimer disease is the leading cause of dementia and the 6th commonest cause of death in the United States...
  35. CELL BIOLOGY OF BIOACTIVE PEPTIDE SECRETION
    Richard E Mains; Fiscal Year: 2013
    ..Kalirin with coronary artery disease, the decrease in Kalirin expression associated with elevated iNOS in Alzheimer disease hippocampus, and the identification of Kalirin as one of the proteins essential for Ras-mediated epigenetic ..
  36. Adipose Tissue Amyloid Precursor Protein and Beta-Amyloid
    William G Tharp; Fiscal Year: 2013
    ....
  37. In Vivo Imaging Alzheimers Disease Pathology with 2-Photon/Lifetime Microscopy
    MOHAMMAD ABBAS YASEEN; Fiscal Year: 2013
    ....
  38. The Role of the Intrinsic Apoptotic Pathway in Familial ALS
    Nichole Reyes; Fiscal Year: 2010
    ..pathogenesis of a number of important neurodegenerative diseases affecting our aging population, including Alzheimer disease, Parkinson disease, and Amyotrophic Lateral Sclerosis (ALS)...
  39. Instrument for Single Molecule Sequencing of Alzheimer's-Relevant Genomic Oxidati
    David E Wolf; Fiscal Year: 2012
    ..types of nucleobase damage Oxidative stress is one of the most earliest and prominent features of Alzheimer disease. Prior work of our collaborator and consultant, Dr. George Perry at University of Texas San Antonio and Dr...
  40. COMPLEMENT AND INFLAMMATORY FACTORS IN AD PATHOGENESIS
    Andrea Joan Tenner; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Alzheimer Disease (AD) is the most common age-related neurodegenerative disorder associated with progressive loss of cognitive function, which currently afflicts up to 5 million people in the US ..
  41. Identifying enhancers with human-specific developmental functions
    James P Noonan; Fiscal Year: 2013
    ..prevalent human diseases with a genetic component, including skin cancers, heart disease, malaria infection, Alzheimer disease, multiple sclerosis and major psychoses, appear to be uncommon, different or absent in chimpanzees...
  42. Multiplexed Protein &miRNA Biomarker-based Next-gen Test for Alzheimers Disease
    ARMIN H REITMAIR; Fiscal Year: 2013
    ....
  43. Neurotrophin Protection in HIV and Aging
    Rick B Meeker; Fiscal Year: 2013
    ..Dendritic beading, pruning and synapse loss are common pathological features of HIV infection, aging and Alzheimer disease. Evidence supports an association between this damage and a loss of neurotrophic support as well as a ..
  44. Role of the MyD88-independent pathway in Alzheimers disease
    Ken Ichiro Fukuchi; Fiscal Year: 2013
    ..The long term goals of this research are to determine the roles of TLR signaling in AD progression and to establish the logical basis for developing safe and effective immunotherapy for AD. ..
  45. An iPS Disease-in-a-Dish Model of Familial Alzheimers
    Terrence Town; Fiscal Year: 2012
    ..control forebrain neurons differentiated from reprogrammed iPS cells. In Sub-Aim 2a, we hypothesize that Alzheimer disease phenotypes will occur and be exacerbated by experimental induction of excitotoxicity in fAD mutant vs...
  46. Upgrade of Our Thermo LTQ to a LTQ Orbitrap XL ETD Mass Spectrometer
    C Robert Matthews; Fiscal Year: 2010
    ..wide range of biological and biomedical areas: (1) the molecular basis of neurodegenerative diseases such as Alzheimer disease and amyotrophic lateral sclerosis;(2) the molecule basis for the immune response to viral diseases;(3) the ..
  47. ApoE4 Structure Correctors as a Therapeutic Approach for Alzheimers Disease
    Robert W Mahley; Fiscal Year: 2013
    ..Probes identified from these studies can be used to further study the role of apoE4 in AD and will serve as a foundation for the development of novel drugs to treat AD. ..
  48. Proteomics of memory: Normal brain aging and Alzheimers Disease
    Catherine Cook Kaczorowski; Fiscal Year: 2013
    ..Robert Vassar at Northwestern University Medical School. Outcomes of the proposed research have the potential to make a major impact on the identification of new treatments for both aging and AD-related memory disorders. ..
  49. New tools to study leukocyte infiltration into the CNS
    CHARLES LEE HOWE; Fiscal Year: 2013
    ..in a wide array of neurologic diseases, including stroke, epilepsy, demyelinating disease, Alzheimer disease, ALS, cancer, pain, TBI, spinal cord injury, and infection...
  50. Identification of Novel Small Molecules as Tau Protein Aggregation Inhibitors for
    ALAN D SNOW; Fiscal Year: 2011
    ..small molecule drugs for the treatment of tau protein aggregation found in the neurofibrillary tangles of Alzheimer disease. Neurofibrillary tangle formation is one of the pathological hallmarks of Alzheimer's disease, the ..
  51. Intersectin Links Amyloidogenic Processes in Alzheimer Disease and Down Syndrome
    Jessica O Wilson; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Alzheimer Disease (AD) plagues our ageing population as the most common cause of cognitive impairment in the elderly and the sixth leading cause of death in America...
  52. Effects of bladder control medication on beta-amyloid peptide metabolism
    Jeremy B Tuttle; Fiscal Year: 2012
    ..applicant): The central hypothesis of this proposal is unusual: Bladder voiding dysfunction associates with Alzheimer disease (AD) and dementia. Animal models of AD voiding problems have not been studied...
  53. Statins To Prevent Progression of Glaucoma: The STOP Glaucoma Trial
    Joshua D Stein; Fiscal Year: 2013
    ..events and may be helpful in diseases of the central nervous system, including ischemic stroke, Alzheimer disease, and multiple sclerosis...
  54. Identification of Persistent Impairments in Postural Control Following Concussion
    GEORGE W SHAVER; Fiscal Year: 2011
    ..sclerosis, mild cognitive impairment, clinically diagnosed depression, and a potentially earlier onset of Alzheimer disease in the long term...
  55. Clathrin-coated vesicles and endocytic function
    Linton M Traub; Fiscal Year: 2013
    ..are linked to several important human disease states, from hypercholesterolemia and certain cancers to Alzheimer disease. Because endocytic clathrin coats are manufactured only to ferry designated cargo into the cytosol, and ..
  56. New Strategy to Fight Selective Cholinergic Neuronal Loss in Alzheimer Disease
    William Z Suo; Fiscal Year: 2013
    ..This finding will provide rationale for trials of M2 receptor blockers for the prevention of cholinergic neurodegeneration in human AD. ..
  57. Frontiers in Lipid Biology
    Dennis E Vance; Fiscal Year: 2012
    ..the risk of atherosclerosis and has been associated with several neurodegenerative diseases such as Alzheimer disease. This unique international conference will address current issues in lipid metabolic processes and their ..
  58. A Phase 2 Trial of AAV-NGF Gene Delivery in Alzheimer's Disease
    Paul S Aisen; Fiscal Year: 2012
    ..of cholinergic neurons of the basal forebrain, a cell population that undergoes extensive degeneration in Alzheimer disease (AD)...
  59. Development of Novel Tricyclic Pyrone Drugs for Treatment of Alzheimer Disease
    Xinmin Simon Xie; Fiscal Year: 2013
    ..Our ultimate goal is to translate our preclinical discovery of the novel TP compounds into clinical therapeutic candidates that possess AD disease-modifying properties. ..
  60. The Role of KCa3.1 in Neuroinflammation in Alzheimer Disease
    Izumi Maezawa; Fiscal Year: 2013
    ....
  61. Mechanisms for NSAID Alzheimer Prevention
    Gregory M Cole; Fiscal Year: 2013
    ..and naproxen and other non-selective cyclooxygenase (COX) inhibitors) are associated with lower risk for Alzheimer Disease (AD)...
  62. Posterior Cingulate Perfusion and Alzheimer Disease Risk
    Sterling C Johnson; Fiscal Year: 2013
    ..Early identification of AD and other dementias will serve to reduce this discrepancy and to relieve the overall economic burden of this disease to the U.S. and the VA health care system. ..
  63. NEURONAL CYTOSKELETAL ALTERATIONS IN ALZHEIMERS DISEASE
    Khalid Iqbal; Fiscal Year: 1999
    DESCRIPTION: Our long term objective is to understand the etiology and the pathogenesis of Alzheimer disease (AD) and to find a rational therapeutic treatment of the disease...
  64. Alzheimers Disease Mechanism & Experimental Therapeutic
    Philip Wong; Fiscal Year: 2009
    ..Furthermore, these studies provide important information regarding potential mechanism based toxicities associated with anti-BACE1 therapy in humans that should be carefully monitored in clinical trials in the future. ..
  65. BIOLOGY OF CHROMOSOME 17 LINKED DEMENTIA WITH TAUOPATHY
    Jill Murrell; Fiscal Year: 2000
    ..In view of the fact that MSTD shares dome molecular pathological characteristics with Alzheimer disease, corticobasal degeneration, and progressive supranuclear palsy, determining the genetic basis of MSTD would ..
  66. DECOMPOSITION OF MEMORY FAILURE IN ALZHEIMERS DISEASE
    John Gabrieli; Fiscal Year: 1999
    ....
  67. SPATIALLY ORIENTED DATABASE FOR DIGITAL BRAIN IMAGES
    Edward H Herskovits; Fiscal Year: 2010
    ..Such predictive models could guide early therapy for Alzheimer disease or stroke, among other diseases, and thus have immense potential...
  68. VITAMIN E TRIAL IN PERSONS WITH DOWN SYNDROME
    Arthur Dalton; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Alzheimer disease (AD) continues to be the most serious health problem faced by aging persons with Down syndrome. AD is also a major public health concern in the aging general population...
  69. NMR SPECTROSCOPY IN ALZHEIMERS DISEASE
    MARIA CASERTA; Fiscal Year: 1999
    ..She will develop didactic courses for residents and clinicians in the biology of AD, and will become a resource for clinical investigators in the field of AD at Northwestern during the five year period of this award. ..
  70. Array Tomographic Single-Synapse Analysis of Normal and Disordered Cortex
    Stephen Smith; Fiscal Year: 2009
    ....
  71. 7th International Conference on Frontotemporal Dementias
    BERNARDINO FRANCESCO GHETTI; Fiscal Year: 2010
    ..of the molecular basis of dementia have led to an understanding of the clinical and neuropathologic basis of Alzheimer disease and of numerous other dementias...
  72. ALZHEIMER DISEASE AMONG SEVENTH-DAY ADVENTISTS
    Zoreh Davanipour; Fiscal Year: 1992
    The proposed population-based, statewide study of Alzheimer disease (AD) among California Seventh-day Adventists is designed to provide incidence/prevalence data and information about risk factors for AD using a case-control methodology...