D J Selkoe

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease
    D J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    Trends Cell Biol 8:447-53. 1998
  2. ncbi Presenilin, Notch, and the genesis and treatment of Alzheimer's disease
    D J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, 77 Avenue Louis Pasteur, HIM 730, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:11039-41. 2001
  3. ncbi Introducing transglutaminase into the study of Alzheimer's disease. A personal look back
    Dennis J Selkoe
    Center for Neurologic Diseases, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, HIM 730, Boston, MA 02115, USA
    Neurochem Int 40:13-6. 2002
  4. 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
  5. ncbi Deciphering the genesis and fate of amyloid beta-protein yields novel therapies for Alzheimer disease
    Dennis J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA
    J Clin Invest 110:1375-81. 2002
  6. ncbi The genetics and molecular pathology of Alzheimer's disease: roles of amyloid and the presenilins
    D J Selkoe
    Department of Neurology and Neuroscience, Harvard Medical School, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Neurol Clin 18:903-22. 2000
  7. ncbi Clearing the brain's amyloid cobwebs
    D J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    Neuron 32:177-80. 2001
  8. ncbi Notch and presenilins in vertebrates and invertebrates: implications for neuronal development and degeneration
    D J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, HIM 730, MA 02115, USA
    Curr Opin Neurobiol 10:50-7. 2000
  9. ncbi Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma
    A L Biere
    Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 271:32916-22. 1996
  10. ncbi The role of APP processing and trafficking pathways in the formation of amyloid beta-protein
    D J Selkoe
    Centre for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Ann N Y Acad Sci 777:57-64. 1996

Collaborators

Detail Information

Publications119 found, 100 shown here

  1. ncbi The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease
    D J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    Trends Cell Biol 8:447-53. 1998
    ..This review discusses the current understanding of the cell biology of two proteins crucial for the pathogenesis of AD, the beta-amyloid precursor protein and presenilin...
  2. ncbi Presenilin, Notch, and the genesis and treatment of Alzheimer's disease
    D J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, 77 Avenue Louis Pasteur, HIM 730, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:11039-41. 2001
    ....
  3. ncbi Introducing transglutaminase into the study of Alzheimer's disease. A personal look back
    Dennis J Selkoe
    Center for Neurologic Diseases, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, HIM 730, Boston, MA 02115, USA
    Neurochem Int 40:13-6. 2002
  4. 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
    ....
  5. ncbi Deciphering the genesis and fate of amyloid beta-protein yields novel therapies for Alzheimer disease
    Dennis J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA
    J Clin Invest 110:1375-81. 2002
  6. ncbi The genetics and molecular pathology of Alzheimer's disease: roles of amyloid and the presenilins
    D J Selkoe
    Department of Neurology and Neuroscience, Harvard Medical School, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Neurol Clin 18:903-22. 2000
    ..In this article, the exciting new understanding of the pathogenesis of AD is reviewed and its affect on the patient population is discussed...
  7. ncbi Clearing the brain's amyloid cobwebs
    D J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    Neuron 32:177-80. 2001
    ..This previously neglected topic has begun receiving serious attention. Understanding how proteolysis regulates Abeta levels in the cerebral cortex has implications for both the pathogenesis and the treatment of this protean disorder...
  8. ncbi Notch and presenilins in vertebrates and invertebrates: implications for neuronal development and degeneration
    D J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, HIM 730, MA 02115, USA
    Curr Opin Neurobiol 10:50-7. 2000
    ....
  9. ncbi Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma
    A L Biere
    Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 271:32916-22. 1996
    ..Abeta distribution in plasma was not significantly influenced by apolipoprotein E genotype. We conclude that Abeta is normally bound to and transported by albumin and specific lipoproteins in human plasma under physiological conditions...
  10. ncbi The role of APP processing and trafficking pathways in the formation of amyloid beta-protein
    D J Selkoe
    Centre for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Ann N Y Acad Sci 777:57-64. 1996
    ..In conclusion, studies of the regulation of A beta production and aggregation in cell culture can provide information under physiological conditions that can complement analyses of these processes in vivo...
  11. ncbi Rapid Notch1 nuclear translocation after ligand binding depends on presenilin-associated gamma-secretase activity
    O Berezovska
    Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA
    Ann N Y Acad Sci 920:223-6. 2000
    ....
  12. ncbi FAD mutations in presenilin-1 or amyloid precursor protein decrease the efficacy of a gamma-secretase inhibitor: evidence for direct involvement of PS1 in the gamma-secretase cleavage complex
    W Xia
    Department of Neurology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Neurobiol Dis 7:673-81. 2000
    ..Taken together, these findings suggest that PS1 participates physically in a complex with APP during the gamma-secretase cleavage event...
  13. ncbi Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta-protein generation
    W Xia
    Department of Neurology and Program in Neuroscience, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 97:9299-304. 2000
    ..Thus, PSs are complexed with the gamma-secretase substrates C83 and C99 in the subcellular locations where Abeta is generated, indicating that PSs are directly involved in the pathogenically critical intramembranous proteolysis of APP...
  14. ncbi Presenilin 1 regulates the processing of beta-amyloid precursor protein C-terminal fragments and the generation of amyloid beta-protein in endoplasmic reticulum and Golgi
    W Xia
    Department of Neurology, Harvard Medical School, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Biochemistry 37:16465-71. 1998
    ..Our results indicate PS1 and APP can interact in the ER and Golgi, where PS1 is required for proper gamma-secretase processing of APP CTFs, and that PS1 mutations augment Abeta42 levels principally in Golgi-like vesicles...
  15. ncbi Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity
    M S Wolfe
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 398:513-7. 1999
    ....
  16. ncbi The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner
    W T Kimberly
    Department of Neurology, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Biol Chem 276:40288-92. 2001
    ..These findings strongly support the hypothesis that APP signals in the nucleus in a manner analogous to the function of Notch...
  17. ncbi Aspartate mutations in presenilin and gamma-secretase inhibitors both impair notch1 proteolysis and nuclear translocation with relative preservation of notch1 signaling
    O Berezovska
    Alzheimer s Disease Research Laboratory, Department of Neurology, Harvard Medical School and Massachusetts General Hospital, Charlestown, California, USA
    J Neurochem 75:583-93. 2000
    ..The latter is an important finding from the perspective of therapeutic treatment of Alzheimer's disease by targeting gamma-secretase processing of APP to reduce Abeta production...
  18. ncbi Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue
    M B Podlisny
    Center for Neurologic Diseases, Harvard Medical School, Boston, Massachusetts, 02115, USA
    Neurobiol Dis 3:325-37. 1997
    ..Our results indicate that presenilins are rapidly processed to N- and C-terminal fragments in both neural and nonneural cells and that interference with this processing is not an obligatory feature of FAD-causing mutations...
  19. ncbi Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme
    K Vekrellis
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Neurosci 20:1657-65. 2000
    ..Our results support a principal role for membrane-associated and secreted IDE isoforms in the degradation and clearance of naturally secreted Abeta by neurons and microglia...
  20. ncbi The AMY antigen co-occurs with abeta and follows its deposition in the amyloid plaques of Alzheimer's disease and down syndrome
    C A Lemere
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts, USA
    Am J Pathol 155:29-37. 1999
    ..We conclude that AMY IR represents an amyloid-associated antigen that co-deposits in most but not all Abeta plaques in AD and DS and that accumulation of the AMY antigen follows Abeta deposition in plaques...
  21. ncbi Evidence that the 42- and 40-amino acid forms of amyloid beta protein are generated from the beta-amyloid precursor protein by different protease activities
    M Citron
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA, USA
    Proc Natl Acad Sci U S A 93:13170-5. 1996
    ....
  22. ncbi Interaction between amyloid precursor protein and presenilins in mammalian cells: implications for the pathogenesis of Alzheimer disease
    W Xia
    Department of Neurology, Harvard Medical School, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 94:8208-13. 1997
    ....
  23. ncbi The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation
    W T Kimberly
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 275:3173-8. 2000
    ..We conclude that presenilins, and their TM aspartates in particular, are attractive targets for lowering Abeta therapeutically to prevent Alzheimer's disease...
  24. ncbi 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...
  25. 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
    ....
  26. ncbi Altered fatty acid composition of dopaminergic neurons expressing alpha-synuclein and human brains with alpha-synucleinopathies
    Ronit Sharon
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 278:49874-81. 2003
    ..Together with our earlier observations, these results suggest that alphaS-PUFA interactions help regulate neuronal PUFA levels as well as the oligomerization state of alphaS, both normally and in human synucleinopathies...
  27. ncbi A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference
    Tracy L Young-Pearse
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 27:14459-69. 2007
    ..We conclude that full-length APP functions as an important factor for proper migration of neuronal precursors into the cortical plate during the development of the mammalian brain...
  28. ncbi The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments
    Matthew J LaVoie
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02215, USA
    J Biol Chem 278:34427-37. 2003
    ..Thus, Notch and its cognate ligands are processed by the same molecular machinery and may antagonistically regulate each other's signaling...
  29. ncbi A de novo designed helix-turn-helix peptide forms nontoxic amyloid fibrils
    Y Fezoui
    Department of Neurology Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Struct Biol 7:1095-9. 2000
    ..These results suggest that the potential to form fibrils under physiologic conditions is not limited to those proteins associated with amyloidoses and that fibril formation alone is not predictive of cytotoxic activity...
  30. ncbi Lysosomal processing of amyloid precursor protein to A beta peptides: a distinct role for cathepsin S
    J S Munger
    Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Biochem J 311:299-305. 1995
    ..This pathway appears to be inducible, distinct from a constitutive pathway used by 293 and other cells to generate A beta, and may be relevant to the pathogenesis of Alzheimer's disease...
  31. ncbi The lysosomal cysteine protease, cathepsin S, is increased in Alzheimer's disease and Down syndrome brain. An immunocytochemical study
    C A Lemere
    Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA
    Am J Pathol 146:848-60. 1995
    ..The association of cat S immunoreactivity with tangle-bearing neurons, astrocytes, and rare senile plaques implies a role for altered cat S activity in the pathogenesis of AD...
  32. ncbi Gamma-secretase exists on the plasma membrane as an intact complex that accepts substrates and effects intramembrane cleavage
    Jay H Chyung
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 280:4383-92. 2005
    ....
  33. ncbi Reducing amyloid plaque burden via ex vivo gene delivery of an Abeta-degrading protease: a novel therapeutic approach to Alzheimer disease
    Matthew L Hemming
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 4:e262. 2007
    ..The objective of this study was to determine if enhancing the clearance of Abeta in the brain by ex vivo gene delivery of an Abeta-degrading protease can reduce amyloid plaque burden...
  34. ncbi The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease
    Ronit Sharon
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02215, USA
    Neuron 37:583-95. 2003
    ..We conclude that alpha S interacts with PUFAs in vivo to promote the formation of highly soluble oligomers that precede the insoluble alpha S aggregates associated with neurodegeneration...
  35. ncbi Enhancer function and novel DNA binding protein activity in the near upstream betaAPP gene promoter
    H W Querfurth
    Division of Neurology, St Elizabeth s Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA
    Gene 232:125-41. 1999
    ..An interaction model involving both domains and looping of interjacent DNA is proposed. We conclude that this newly described binding protein-enhancer complex is required for full betaAPP promoter activation...
  36. ncbi Nasal vaccination with beta-amyloid peptide for the treatment of Alzheimer's disease
    C A Lemere
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    DNA Cell Biol 20:705-11. 2001
    ..Examples of other intranasal vaccines and mucosal adjuvants are presented. Taken together, these data have implications for the future development of an intranasal Abeta vaccine for humans...
  37. ncbi Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice
    M Citron
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Nat Med 3:67-72. 1997
    ..Our data demonstrate that the presenilin mutations cause a dominant gain of function and may induce AD by enhancing A beta 42 production, thus promoting cerebral beta-amyloidosis...
  38. ncbi gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins
    Dominic M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Biochemistry 42:6664-73. 2003
    ....
  39. ncbi Alzheimer's disease: genes, proteins, and therapy
    D J Selkoe
    Department of Neurology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
    Physiol Rev 81:741-66. 2001
    ..The progress reviewed here, coupled with better ability to diagnose the disease early, bode well for the successful development of therapeutic and preventative drugs for this major public health problem...
  40. ncbi Amyloid beta-protein and the genetics of Alzheimer's disease
    D J Selkoe
    Department of Neurology and Program in Neuroscience, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 271:18295-8. 1996
  41. ncbi alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins
    R Sharon
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:9110-5. 2001
    ....
  42. ncbi In vitro studies of amyloid beta-protein fibril assembly and toxicity provide clues to the aetiology of Flemish variant (Ala692-->Gly) Alzheimer's disease
    D M Walsh
    Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston MA 02115, USA
    Biochem J 355:869-77. 2001
    ..Increased peptide solubility and assembly stability would favour formation of larger deposits and inhibit their elimination. In addition, increased concentrations of neurotoxic assemblies would accelerate neuronal injury and death...
  43. ncbi Regulation of rat magnocellular neurosecretory system by D-aspartate: evidence for biological role(s) of a naturally occurring free D-amino acid in mammals
    H Wang
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    J Endocrinol 167:247-52. 2000
    ..These results provide evidence for the role(s) of naturally occurring free D-Asp in mammalian physiology. The findings argue against the conventional concept that only L-stereoisomers of amino acids are functional in higher species...
  44. ncbi Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation
    W Q Qiu
    Department of Neurology and Program in Neuroscience, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115 5716, USA
    J Biol Chem 273:32730-8. 1998
    ..We conclude that a principal protease capable of down-regulating the levels of secreted Abeta extracellularly is IDE...
  45. ncbi Inhibition of receptor-mediated endocytosis demonstrates generation of amyloid beta-protein at the cell surface
    Jay H Chyung
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:51035-43. 2003
    ..Our findings are consistent with a role for the gamma-secretase complex in the processing of numerous single-transmembrane receptors at the cell surface...
  46. ncbi Notch and the amyloid precursor protein are cleaved by similar gamma-secretase(s)
    W Taylor Kimberly
    Center for Neurologic Diseases, Brigham and Women's Hospital, and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Biochemistry 42:137-44. 2003
    ..These data resolve some of the apparent conflicts and strongly indicate that Notch and APP are proteolyzed by the same enzyme(s)...
  47. ncbi Effects of prolonged angiotensin-converting enzyme inhibitor treatment on amyloid beta-protein metabolism in mouse models of Alzheimer disease
    Matthew L Hemming
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Neurobiol Dis 26:273-81. 2007
    ..Furthermore, we find no change in plaque deposition or in peripheral Abeta levels. Data from these Alzheimer models suggest that captopril and similar ACE inhibitors do not cause Abeta accumulation in vivo...
  48. ncbi Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking
    Andreas Weihofen
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 48:2045-52. 2009
    ..Finally, we find that Miro and Milton expression suppresses altered mitochondrial morphology induced by loss of Pink1 function in cell culture. Our findings suggest that Pink1 functions in the trafficking of mitochondria in cells...
  49. ncbi Detergent-dependent dissociation of active gamma-secretase reveals an interaction between Pen-2 and PS1-NTF and offers a model for subunit organization within the complex
    Patrick C Fraering
    Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 43:323-33. 2004
    ..Taken together, our results demonstrate that Pen-2 interacts with PS-NTF within active gamma-secretase and offer a model for how the components of active gamma-secretase interact physically with each other...
  50. ncbi Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein
    Wesley Farris
    Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
    Am J Pathol 164:1425-34. 2004
    ..Our findings have relevance for the emerging genetic evidence suggesting that IDE may be a late-onset AD-risk gene, and for the epidemiological relationships among hyperinsulinemia, DM2, and AD...
  51. ncbi Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers
    Matthew Townsend
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA
    Ann Neurol 60:668-76. 2006
    ..INTERPRETATION: A small, orally available natural product penetrates into the brain in vivo to rescue the memory impairment produced by soluble Abeta oligomers through a mechanism that restores hippocampal synaptic plasticity...
  52. ncbi Effects of secreted oligomers of amyloid beta-protein on hippocampal synaptic plasticity: a potent role for trimers
    Matthew Townsend
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA
    J Physiol 572:477-92. 2006
    ..We conclude that specific assemblies, particularly timers, of naturally secreted Abeta oligomers are potent and selective inhibitors of certain forms of hippocampal LTP...
  53. ncbi Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1
    Andreas Weihofen
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Hum Mol Genet 17:602-16. 2008
    ..Finally, we document the influence of Parkin on Pink1 subcellular distribution, providing further evidence for a common pathogenic pathway in recessive PD...
  54. ncbi Immune hyporesponsiveness to amyloid beta-peptide in amyloid precursor protein transgenic mice: implications for the pathogenesis and treatment of Alzheimer's disease
    A Monsonego
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, HIM 730, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:10273-8. 2001
    ..Moreover, humans with life-long elevation of brain and peripheral Abeta (e.g., patients with presenilin mutations or Down syndrome) could have reduced immune responses to Abeta vaccination...
  55. ncbi Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition
    D M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA
    Biochem Soc Trans 30:552-7. 2002
    ....
  56. ncbi Evidence for genetic linkage of Alzheimer's disease to chromosome 10q
    L Bertram
    Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Science 290:2302-3. 2000
    ..Furthermore, we found evidence for allele-specific association between the putative disease locus and marker D10S583, which has recently been located within 195 kilobases of the IDE gene...
  57. ncbi Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease
    Alon Monsonego
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 112:415-22. 2003
    ....
  58. ncbi Soluble Abeta inhibits specific signal transduction cascades common to the insulin receptor pathway
    Matthew Townsend
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 282:33305-12. 2007
    ....
  59. ncbi Purification and characterization of the human gamma-secretase complex
    Patrick C Fraering
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 43:9774-89. 2004
    ....
  60. ncbi Toward a remembrance of things past: deciphering Alzheimer disease
    Dennis J Selkoe
    Department of Neurology, Harvard Medical School, USA
    Harvey Lect 99:23-45. 2003
  61. ncbi Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway
    Ganesh M Shankar
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 27:2866-75. 2007
    ..Our approach provides a quantitative cellular model for elucidating the molecular basis of Abeta-induced neuronal dysfunction...
  62. ncbi A profile of impaired insulin degradation in relation to late-life cognitive decline: a preliminary investigation
    Olivia I Okereke
    Division of Aging, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Int J Geriatr Psychiatry 24:177-82. 2009
    ..In preliminary analyses, we considered the relation of combined lower insulin secretion (c-peptide) and higher insulin--possibly a phenotype for impaired insulin degradation--to cognitive decline...
  63. ncbi Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo
    Wesley Farris
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:4162-7. 2003
    ....
  64. ncbi HLA-DR alleles in amyloid beta-peptide autoimmunity: a highly immunogenic role for the DRB1*1501 allele
    Victor Zota
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA, USA
    J Immunol 183:3522-30. 2009
    ..This new knowledge enables us to explore the basis for understanding the variations in naturally occurring Abeta-reactive T cells and Abeta immunogenicity among humans...
  65. ncbi Aph-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates
    Allen C Chen
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 285:11378-91. 2010
    ..Taken together, our data suggest a dominant role for Aph-1 in interacting with gamma-secretase substrates prior to their processing by the proteolytic complex...
  66. ncbi Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein
    D J Selkoe
    Department of Neurology, Harvard Medical School, and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Ann N Y Acad Sci 924:17-25. 2000
    ..Mounting evidence from many laboratories supports an A beta accumulation in limbic and association cortices as the fundamental initiator of the disease, with attendant therapeutic implications...
  67. ncbi Are presenilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's disease
    M S Wolfe
    Department of Pharmaceutical Sciences, University of Tennessee, Memphis 38163, USA
    Biochemistry 38:11223-30. 1999
    ..Thus, presenilins and S2P appear to be members of a new type of polytopic protease with an intramembranous active site...
  68. ncbi Diffuse plaques contain C-terminal A beta 42 and not A beta 40: evidence from cats and dogs
    B J Cummings
    Laboratories for Molecular Neuroscience, McLean Hospital, Harvard Medical School, Belmont, MA 02178 USA
    Neurobiol Aging 17:653-9. 1996
    ..However, not all neuritic plaques contain A beta 40 epitopes...
  69. ncbi The role of cell-derived oligomers of Abeta in Alzheimer's disease and avenues for therapeutic intervention
    D M Walsh
    Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Republic of Ireland
    Biochem Soc Trans 33:1087-90. 2005
    ..In each case, compounds capable of reducing oligomer production or antibodies that avidly bind Abeta oligomers also ameliorate the synaptotoxic effects of these natural, cell-derived oligomers...
  70. ncbi Amyloid deposition is associated with impaired default network function in older persons without dementia
    Reisa A Sperling
    Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Neuron 63:178-88. 2009
    ....
  71. ncbi Presenilin: running with scissors in the membrane
    Dennis J Selkoe
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cell 131:215-21. 2007
    ..Here we highlight recent progress in deciphering the role of presenilin/gamma-secretase in biology and medicine and pose key questions for future study...
  72. ncbi Dopamine covalently modifies and functionally inactivates parkin
    Matthew J LaVoie
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, 77 Avenue Louis Pasteur, HIM 7th Floor, Boston, Massachusetts 02115, USA
    Nat Med 11:1214-21. 2005
    ....
  73. ncbi Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation
    W Taylor Kimberly
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
    J Neurosci 25:5533-43. 2005
    ..We conclude that endogenous AICD undergoes tight temporal regulation during the differentiation of neurons and is negatively regulated by JNK3 via phosphorylation of APP at Thr668...
  74. ncbi Ten-year change in plasma amyloid beta levels and late-life cognitive decline
    Olivia I Okereke
    Division of Aging and Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 181 Longwood Ave, Third Floor, Boston, MA 02115, USA
    Arch Neurol 66:1247-53. 2009
    ..Plasma levels of amyloid beta peptide (Abeta) are potential biomarkers of early cognitive impairment and decline and of Alzheimer disease risk...
  75. ncbi Amyloid beta-peptide is produced by cultured cells during normal metabolism: a reprise
    Dennis J Selkoe
    Center for Neurologic Diseases, Harvard Institutes of Medicine, Rm 730, 77 Avenue Louis Pasteur, Boston MA 02115, USA
    J Alzheimers Dis 9:163-8. 2006
    ..Here, I review the background underlying this discovery and then discuss its implications for research on Alzheimer's disease, particularly for the development of disease-modifying therapies...
  76. ncbi Performance characteristics of plasma amyloid-beta 40 and 42 assays
    Olivia I Okereke
    Division of Aging, Department of Medicine, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02115, USA
    J Alzheimers Dis 16:277-85. 2009
    ..While these preliminary findings suggest that measuring plasma Abeta(40) and Abeta(42) may be feasible in varied research settings, additional work in this area is necessary...
  77. ncbi A specific enzyme-linked immunosorbent assay for measuring beta-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer disease
    Weiming Xia
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, HIM 616, 77 Ave Louis Pasteur, Boston, MA 02115, USA
    Arch Neurol 66:190-9. 2009
    ....
  78. ncbi Functional alterations in memory networks in early Alzheimer's disease
    Reisa A Sperling
    Department of Neurology, Center for Alzheimer s Research and Treatment, Brigham and Women s Hospital, 221 Longwood Avenue, Boston, MA 02115, USA
    Neuromolecular Med 12:27-43. 2010
    ..Research is ongoing to determine if these early network alterations will serve as sensitive predictors of clinical decline, and eventually, as markers of pharmacological response to potential disease-modifying treatments for AD...
  79. ncbi Secreted APP regulates the function of full-length APP in neurite outgrowth through interaction with integrin beta1
    Tracy L Young-Pearse
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Neural Dev 3:15. 2008
    ....
  80. ncbi Loss of neprilysin function promotes amyloid plaque formation and causes cerebral amyloid angiopathy
    Wesley Farris
    Center for Neurologic Diseases, Department of Neurology, Harvard Institutes of Medicine, Room 730, Boston, MA 02115, USA
    Am J Pathol 171:241-51. 2007
    ....
  81. ncbi Biochemical and functional interaction of disrupted-in-schizophrenia 1 and amyloid precursor protein regulates neuronal migration during mammalian cortical development
    Tracy L Young-Pearse
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 30:10431-40. 2010
    ....
  82. ncbi Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior
    Dennis J Selkoe
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Behav Brain Res 192:106-13. 2008
    ..A new diagnostic-therapeutic paradigm to successfully address AD and its harbinger, mild cognitive impairment-amnestic type, is emerging...
  83. ncbi Alternative splicing of human insulin-degrading enzyme yields a novel isoform with a decreased ability to degrade insulin and amyloid beta-protein
    Wesley Farris
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 44:6513-25. 2005
    ..Our results identify a novel, catalytically inefficient form of IDE expressed in brain and non-neural tissues and recommend novel regions of the IDE gene in which to search for mutations predisposing patients to AD and DM2...
  84. ncbi Biochemistry. Intramembrane proteases--mixing oil and water
    Michael S Wolfe
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA
    Science 296:2156-7. 2002
  85. ncbi Folding proteins in fatal ways
    Dennis J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 426:900-4. 2003
    ..Understanding some of the principles of protein folding has helped to explain how such diseases arise, with attendant therapeutic insights...
  86. ncbi Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death
    Malcolm A Leissring
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Harvard Medical School, Boston, MA 02115, USA
    Neuron 40:1087-93. 2003
    ..Our findings demonstrate that chronic upregulation of Abeta-degrading proteases represents an efficacious therapeutic approach to combating Alzheimer-type pathology in vivo...
  87. ncbi Evidence for peripheral clearance of cerebral Abeta protein following chronic, active Abeta immunization in PSAPP mice
    Cynthia A Lemere
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Neurobiol Dis 14:10-8. 2003
    ..Most of the Abeta in the serum of the immunized mice was bound to antibodies. We conclude that following active immunization, anti-Abeta antibodies sequester serum Abeta and may increase central nervous system to serum Abeta clearance...
  88. ncbi Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies
    Michael G Schlossmacher
    Department of Neurology, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Am J Pathol 160:1655-67. 2002
    ..These results suggest that functional parkin proteins may be required during LB formation...
  89. ncbi Activity-dependent isolation of the presenilin- gamma -secretase complex reveals nicastrin and a gamma substrate
    William P Esler
    Center for Neurologic Diseases, Brigham and Women's Hospital and Program in Neuroscience, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:2720-5. 2002
    ....
  90. ncbi Proteolysis of chimeric beta-amyloid precursor proteins containing the Notch transmembrane domain yields amyloid beta-like peptides
    Jimin Zhang
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 277:15069-75. 2002
    ..We conclude that gamma-secretase can cleave near the middle of the Notch TMD, that Abeta-like peptides may arise during Notch processing, and that the pre-TMD sequence of the substrate influences recognition or binding by the enzyme...
  91. ncbi Developing preventive therapies for chronic diseases: lessons learned from Alzheimer's disease
    Dennis J Selkoe
    Harvard Medical School, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nutr Rev 65:S239-43. 2007
    ..While hard work lies ahead, the movement from basic research to the clinic in AD represents a triumph of reductionist biology applied to the most complex of all biological systems, the human cerebral cortex...
  92. ncbi Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration
    Dominic M Walsh
    Department of Neurology, Harvard Medical School, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Protein Pept Lett 11:213-28. 2004
    ..With particular reference to AD and PD, we review recent evidence that soluble oligomers are the principal pathogenic species that drive neuronal dysfunction...
  93. ncbi Alzheimer's disease abeta vaccine reduces central nervous system abeta levels in a non-human primate, the Caribbean vervet
    Cynthia A Lemere
    Center for Neurologic Diseases, HIM 622, Department of Neurology, Brigham and Women s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02215, USA
    Am J Pathol 165:283-97. 2004
    ..The findings further support Abeta immunotherapy as a potential prevention and treatment of AD...
  94. ncbi Deciphering the genetic basis of Alzheimer's disease
    Dennis J Selkoe
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Annu Rev Genomics Hum Genet 3:67-99. 2002
    ..This understanding of the genotype-to-phenotype conversions of familial AD has led to the development of pharmacological strategies to lower amyloid beta-protein levels as a way of treating or preventing all forms of the disease...
  95. ncbi Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics
    Dennis J Selkoe
    Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Annu Rev Pharmacol Toxicol 43:545-84. 2003
    ....
  96. ncbi Deciphering the molecular basis of memory failure in Alzheimer's disease
    Dominic M Walsh
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Neuron 44:181-93. 2004
    ..Accordingly, attempts to slow memory and cognitive loss by decreasing cerebral Abeta levels have entered human trials...
  97. ncbi Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases
    Dennis J Selkoe
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Nat Cell Biol 6:1054-61. 2004
    ..A common theme has arisen in this field: normally-soluble proteins accumulate, misfold and oligomerize, inducing cytotoxic effects that are particularly devastating in the post-mitotic milieu of the neuron...
  98. ncbi Certain inhibitors of synthetic amyloid beta-peptide (Abeta) fibrillogenesis block oligomerization of natural Abeta and thereby rescue long-term potentiation
    Dominic M Walsh
    Department of Neurology, Harvard Medical School, and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115-5716, USA
    J Neurosci 25:2455-62. 2005
    ....
  99. ncbi Aging, amyloid, and Alzheimer's disease: a perspective in honor of Carl Cotman
    Dennis J Selkoe
    Center for Neurological Diseases, Brigham and Women s Hospital, and the Harvard Center for Neurodegeneration and Repair Boston, Massachusetts, USA
    Neurochem Res 28:1705-13. 2003
    ..Some of these are now reaching the clinic, providing the final and most important test for this hypothetical mechanism of disease...
  100. ncbi The E280A presenilin 1 Alzheimer mutation produces increased A beta 42 deposition and severe cerebellar pathology
    C A Lemere
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nat Med 2:1146-50. 1996
    ....
  101. ncbi Assembly of the gamma-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin
    Matthew J LaVoie
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 278:37213-22. 2003
    ....