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Cited by 1,750Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Alzheimer's Disease and the Amyloid-β Peptide

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Murphy, M. Paul, LeVine, Harry·2010·Journal of Alzheimer's Disease
DOI 10.3233/jad-2010-1221PMC PMC2813509
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Abstract

Alzheimer's disease (AD) pathogenesis is widely believed to be driven by the production and deposition of the amyloid-beta peptide (Abeta). For many years, investigators have been puzzled by the weak to nonexistent correlation between the amount of neuritic plaque pathology in the human brain and the degree of clinical dementia. Recent advances in our understanding of the development of amyloid pathology have helped solve this mystery. Substantial evidence now indicates that the solubility of Abeta, and the quantity of Abeta in different pools, may be more closely related to disease state. The composition of these pools of Abeta reflects different populations of amyloid deposits and has definite correlates with the clinical status of the patient. Imaging technologies, including new amyloid imaging agents based on the chemical structure of histologic dyes, are now making it possible to track amyloid pathology along with disease progression in the living patient. Interestingly, these approaches indicate that the Abeta deposited in AD is different from that found in animal models. In general, deposited Abeta is more easily cleared from the brain in animal models and does not show the same physical and biochemical characteristics as the amyloid found in AD. This raises important issues regarding the development and testing of future therapeutic agents.

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  • Amyloid-β plaques or aggregates are key contributors to Alzheimer's disease and are associated with neurotoxicity and neuron dysfunction.

    “Aβ plagues or aggregates are considered as one of the key contributors to AD and they are associated with neurotoxicity and neuron dysfunction.41”

    From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [41]

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  1. [3]Holtzman DM Alzheimer’s disease: Moving towards a vaccine Nature 2008 454 418 420 18650906
  2. [4]Collinge J Clarke AR A general model of prion strains and their pathogenicity Science 2007 318 930 936 17991853
  3. [5]Aguzzi A Sigurdson C Heikenwaelder M Molecular mechanisms of prion pathogenesis Annu Rev Pathol 2008 3 11 40 18233951
  4. [6]Glenner GG Wong CW Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein Biochem. Biophys. Res. Commun 1984 122 1131 1135 6236805
  5. [7]Masters CL Multhaup G Simms G Pottgiesser J Martins RN Beyreuther K Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels EMBO J 1985 4 2757 2763 4065091 PMC554575
  6. [8]Masters CL Simms G Weinman NA Multhaup G McDonald BL Beyreuther K Amyloid plaque core protein in Alzheimer disease and Down syndrome PNAS 1985 82 4245 4249 3159021 PMC397973
  7. [9]Selkoe DJ Alzheimer’s disease: genes, proteins, and therapy Physiol Rev 2001 81 741 766 11274343
  8. [11]Gao Y Pimplikar SW The gamma-secretase-cleaved C-terminal fragment of amyloid precursor protein mediates signaling to the nucleus Proc Natl Acad Sci U S A 2001 98 14979 14984 11742091 PMC64969
  9. [12]Kimberly WT Zheng JB Guenette SY Selkoe DJ The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner J Biol Chem 2001 276 40288 40292 11544248
  10. [14]Rochette MJ Murphy MP Gamma-Secretase: substrates and inhibitors Mol Neurobiol 2002 26 81 95 12392058
  11. [15]Sato T Diehl TS Narayanan S Funamoto S Ihara Y De Strooper B Steiner H Haass C Wolfe MS Active gamma-secretase complexes contain only one of each component J Biol Chem 2007 282 33985 33993 17911105
  12. [16]Wolfe MS Xia W Ostaszewski BL Diehl TS Kimberly WT Selkoe DJ Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity Nature 1999 398 513 517 10206644
  13. [17]Li YM Xu M Lai MT Huang Q Castro JL DiMuzio-Mower J Harrison T Lellis C Nadin A Neduvelil JG Register RB Sardana MK Shearman MS Smith AL Shi XP Yin KC Shafer JA Gardell SJ Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1 Nature 2000 405 689 694 10864326
  14. [18]Shah S Lee SF Tabuchi K Hao YH Yu C LaPlant Q Ball H Dann CE 3rd Sudhof T Yu G Nicastrin functions as a gamma-secretase-substrate receptor Cell 2005 122 435 447 16096062
  15. [19]Kimberly WT LaVoie MJ Ostaszewski BL Ye W Wolfe MS Selkoe DJ Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2 Proc Natl Acad Sci U S A 2003 100 6382 6387 12740439 PMC164455
  16. [20]Edbauer D Winkler E Regula JT Pesold B Steiner H Haass C Reconstitution of gamma-secretase activity Nat Cell Biol 2003 5 486 488 12679784
  17. [21]Selkoe DJ Wolfe MS Presenilin: running with scissors in the membrane Cell 2007 131 215 221 17956719
  18. [22]Murphy MP Hickman LJ Eckman CB Uljon SN Wang R Golde TE gamma-Secretase, evidence for multiple proteolytic activities and influence of membrane positioning of substrate on generation of amyloid beta peptides of varying length J Biol Chem 1999 274 11914 11923 10207012
  19. [23]Lichtenthaler SF Beher D Grimm HS Wang R Shearman MS Masters CL Beyreuther K The intramembrane cleavage site of the amyloid precursor protein depends on the length of its transmembrane domain Proc Natl Acad Sci U S A 2002 99 1365 1370 11805291 PMC122196
  20. [25]Suzuki N Cheung TT Cai X-D Odaka A Otvos L Eckman C Golde TE Younkin SG An increased percentage of long amyloid ß protein is secreted by familial amyloid ß protein precursor (ßAPP717) mutants Science 1994 264 1336 1340 8191290
  21. [26]Kukar T Murphy MP Eriksen JL Sagi SA Weggen S Smith TE Ladd T Khan MA Kache R Beard J Dodson M Merit S Ozols VV Anastasiadis PZ Das P Fauq A Koo EH Golde TE Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production Nat Med 2005 11 545 550 15834426
  22. [28]Hussain I Powell D Howlett DR Tew DG Meek TD Chapman C Gloger IS Murphy KE Southan CD Ryan DM Smith TS Simmons DL Walsh FS Dingwall C Christie G Identification of a Novel Aspartic Protease (Asp 2) as beta-Secretase Mol Cell Neurosci 1999 14 419 427 10656250
  23. [29]Sinha S Anderson JP Barbour R Basi GS Caccavello R Davis D Doan M Dovey HF Frigon N Hong J Jacobson-Croak K Jewett N Keim P Knops J Lieberburg I Power M Tan H Tatsuno G Tung J Schenk D Seubert P Suomensaari SM Wang S Walker D John V Purification and cloning of amyloid precursor protein beta-secretase from human brain Nature 1999 402 537 540 10591214
  24. [30]Yan R Bienkowski MJ Shuck ME Miao H Tory MC Pauley AM Brashier JR Stratman NC Mathews WR Buhl AE Carter DB Tomasselli AG Parodi LA Heinrikson RL Gurney ME Membrane-anchored aspartyl protease with Alzheimer’s disease beta-secretase activity Nature 1999 402 533 537 10591213
  25. [31]Lin X Koelsch G Wu S Downs D Dashti A Tang J Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein Proc Natl Acad Sci U S A 2000 97 1456 1460 10677483 PMC26455
  26. [32]Saunders AJ Kim T-W Tanzi RE Fan W Bennett BD Safura B-K Luo Y Louis J-C McCaleb M Citron M Vassar R Richards WG BACE maps to chromosome 11 and a BACE homolog, BACE2, reside in the obligate Down syndrome region of chromosome 21 Science 1999 286 1255
  27. [33]Bennett BD Babu-Khan S Loeloff R Louis JC Curran E Citron M Vassar R Expression analysis of BACE2 in brain and peripheral tissues J Biol Chem 2000 275 20647 20651 10749877
  28. [34]Marcinkiewicz M Seidah NG Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain J Neurochem 2000 75 2133 2143 11032903
  29. [35]Cai H Wang Y McCarthy D Wen H Borchelt DR Price DL Wong PC BACE1 is the major beta-secretase for generation of Abeta peptides by neurons Nat Neurosci 2001 4 233 234 11224536
  30. [36]Luo Y Bolon B Kahn S Bennett BD Babu-Khan S Denis P Fan W Kha H Zhang J Gong Y Martin L Louis J-C Yan Q Richards WG Citron M Vassar R Mice deficient in BACE1, the Alzheimer’s beta-secretase, have normal phenotype and abolished beta-amyloid generation Nat Neurosci 2001 4 231 232 11224535
  31. [38]Dominguez D Tournoy J Hartmann D Huth T Cryns K Deforce S Serneels L Camacho IE Marjaux E Craessaerts K Roebroek AJ Schwake M D’Hooge R Bach P Kalinke U Moechars D Alzheimer C Reiss K Saftig P De Strooper B Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice J Biol Chem 2005 280 30797 30806 15987683
  32. [39]Hussain I Powell DJ Howlett DR Chapman GA Gilmour L Murdock PR Tew DG Meek TD Chapman C Schneider K Ratcliffe SJ Tattersall D Testa TT Southan C Ryan DM Simmons DL Walsh FS Dingwall C Christie G ASP1 (BACE2) cleaves the amyloid precursor protein at the beta- secretase site Mol Cell Neurosci 2000 16 609 619 11083922
  33. [40]Farzan M Schnitzler CE Vasilieva N Leung D Choe H BACE2, a beta-secretase homolog, cleaves at the beta-site and within the amyloid-beta region of the amyloid-beta precursor protein PNAS 2000 97 9712 9717 10931940 PMC16930
  34. [41]Yan R Munzner JB Shuck ME Bienkowski MJ BACE2 functions as an alternative alpha-secretase in cells J Biol Chem 2001 276 34019 34027 11423558
  35. [42]Basi G Frigon N Barbour R Doan T Gordon G McConlogue L Sinha S Zeller M Antagonistic effects of beta-site amyloid precursor protein-cleaving enzymes 1 and 2 on beta-amyloid peptide production in cells J Biol Chem 2003 278 31512 31520 12801932
  36. [43]Sun X Wang Y Qing H Christensen MA Liu Y Zhou W Tong Y Xiao C Huang Y Zhang S Liu X Song W Distinct transcriptional regulation and function of the human BACE2 and BACE1 genes Faseb J 2005 19 739 749 15857888
  37. [44]Holsinger RM McLean CA Beyreuther K Masters CL Evin G Increased expression of the amyloid precursor beta-secretase in Alzheimer’s disease Ann Neurol 2002 51 783 786 12112088
  38. [45]Fukumoto H Cheung BS Hyman BT Irizarry MC beta-Secretase Protein and Activity Are Increased in the Neocortex in Alzheimer Disease Arch Neurol 2002 59 1381 1389 12223024
  39. [46]Yang LB Lindholm K Yan R Citron M Xia W Yang XL Beach T Sue L Wong P Price D Li R Shen Y Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease Nat Med 2003 9 3 4 12514700
  40. [47]Li R Lindholm K Yang LB Yue X Citron M Yan R Beach T Sue L Sabbagh M Cai H Wong P Price D Shen Y Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer’s disease patients Proc Natl Acad Sci U S A 2004 101 3632 3637 14978286 PMC373514
  41. [49]Hook VY Kindy M Hook G Inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein J Biol Chem 2008 283 7745 7753 18184658
  42. [50]Schechter I Ziv E Kinetic properties of cathepsin D and BACE 1 indicate the need to search for additional beta-secretase candidate(s) Biol Chem 2008 389 313 320 18177262
  43. [51]Iwata N Tsubuki S Takaki Y Watanabe K Sekiguchi M Hosoki E Kawashima-Morishima M Lee HJ Hama E Sekine-Aizawa Y Saido TC Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition Nat Med 2000 6 143 150 10655101
  44. [52]Iwata N Tsubuki S Takaki Y Shirotani K Lu B Gerard NP Gerard C Hama E Lee HJ Saido TC Metabolic regulation of brain Abeta by neprilysin Science 2001 292 1550 1552 11375493
  45. [53]Marr RA Rockenstein E Mukherjee A Kindy MS Hersh LB Gage FH Verma IM Masliah E Neprilysin gene transfer reduces human amyloid pathology in transgenic mice J Neurosci 2003 23 1992 1996 12657655 PMC6742010
  46. [54]Miller BC Eckman EA Sambamurti K Dobbs N Chow KM Eckman CB Hersh LB Thiele DL Amyloid-beta peptide levels in brain are inversely correlated with insulysin activity levels in vivo Proc Natl Acad Sci U S A 2003 100 6221 6226 12732730 PMC156353
  47. [55]Huang SM Mouri A Kokubo H Nakajima R Suemoto T Higuchi M Staufenbiel M Noda Y Yamaguchi H Nabeshima T Saido TC Iwata N Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function J Biol Chem 2006 281 17941 17951 16636059
  48. [56]Qiu WQ Walsh DM Ye Z Vekrellis K Zhang J Podlisny MB Rosner MR Safavi A Hersh LB Selkoe DJ Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation J Biol Chem 1998 273 32730 32738 9830016
  49. [57]Vekrellis K Ye Z Qiu WQ Walsh D Hartley D Chesneau V Rosner MR Selkoe DJ Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme J Neurosci 2000 20 1657 1665 10684867 PMC6772918
  50. [58]Qiu WQ Folstein MF Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer’s disease: review and hypothesis Neurobiol Aging 2006 27 190 198 16399206
  51. [59]Luchsinger JA Tang MX Shea S Mayeux R Hyperinsulinemia and risk of Alzheimer disease Neurology 2004 63 1187 1192 15477536
  52. [60]Caccamo A Oddo S Sugarman MC Akbari Y LaFerla FM Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders Neurobiol Aging 2005 26 645 654 15708439
  53. [61]Miners JS Van Helmond Z Chalmers K Wilcock G Love S Kehoe PG Decreased expression and activity of neprilysin in Alzheimer disease are associated with cerebral amyloid angiopathy J Neuropathol Exp Neurol 2006 65 1012 1021 17021406
  54. [62]Maruyama M Higuchi M Takaki Y Matsuba Y Tanji H Nemoto M Tomita N Matsui T Iwata N Mizukami H Muramatsu S Ozawa K Saido TC Arai H Sasaki H Cerebrospinal fluid neprilysin is reduced in prodromal Alzheimer’s disease Ann Neurol 2005 57 832 842 15929037
  55. [64]Van Uden E Mallory M Veinbergs I Alford M Rockenstein E Masliah E Increased extracellular amyloid deposition and neurodegeneration in human amyloid precursor protein transgenic mice deficient in receptor-associated protein J Neurosci 2002 22 9298 9304 12417655 PMC6758061
  56. [65]Shibata M Yamada S Kumar SR Calero M Bading J Frangione B Holtzman DM Miller CA Strickland DK Ghiso J Zlokovic BV Clearance of Alzheimer’s amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier J Clin Invest 2000 106 1489 1499 11120756 PMC387254
  57. [66]Deane R Du Yan S Submamaryan RK LaRue B Jovanovic S Hogg E Welch D Manness L Lin C Yu J Zhu H Ghiso J Frangione B Stern A Schmidt AM Armstrong DL Arnold B Liliensiek B Nawroth P Hofman F Kindy M Stern D Zlokovic B RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain Nat Med 2003 9 907 913 12808450
  58. [67]DeMattos RB Bales KR Cummins DJ Paul SM Holtzman DM Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer’s disease Science 2002 295 2264 2267 11910111
  59. [68]Zlokovic BV Neurovascular mechanisms of Alzheimer’s neurodegeneration Trends Neurosci 2005 28 202 208 15808355
  60. [69]Roher AE Chaney MO Kuo YM Webster SD Stine WB Haverkamp LJ Woods AS Cotter RJ Tuohy JM Krafft GA Bonnell BS Emmerling MR Morphology and toxicity of Abeta-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer’s disease J. Biol. Chem 1996 271 20631 20635 8702810
  61. [70]Roher A Wolfe D Palutke M KuKuruga D Purification, ultrastructure, and chemical analysis of Alzheimer disease amyloid plaque core protein Proc Natl Acad Sci U S A 1986 83 2662 2666 3458224 PMC323359
  62. [71]Hasegawa M Biochemistry and molecular biology of tauopathies Neuropathology 2006 26 484 490 17080729
  63. [72]Steinerman JR Irizarry M Scarmeas N Raju S Brandt J Albert M Blacker D Hyman B Stern Y Distinct pools of beta-amyloid in Alzheimer disease-affected brain: a clinicopathologic study Arch Neurol 2008 65 906 912 18625856 PMC2586606
  64. [73]Murphy MP Beckett TL Ding Q Patel E Markesbery WR St Clair DK LeVine H 3rd Keller JN Abeta solubility and deposition during AD progression and in APPxPS-1 knock-in mice Neurobiol Dis 2007 27 301 311 17651976 PMC13252904
  65. [74]Dickson TC Vickers JC The morphological phenotype of beta-amyloid plaques and associated neuritic changes in Alzheimer’s disease Neuroscience 2001 105 99 107 11483304
  66. [75]O’Nuallain B Wetzel R Conformational Abs recognizing a generic amyloid fibril epitope Proc Natl Acad Sci U S A 2002 99 1485 1490 11818542 PMC122217
  67. [76]Lambert MP Velasco PT Chang L Viola KL Fernandez S Lacor PN Khuon D Gong Y Bigio EH Shaw P De Felice FG Krafft GA Klein WL Monoclonal antibodies that target pathological assemblies of Abeta J Neurochem 2007 100 23 35 17116235
  68. [77]Nilsson KP Aslund A Berg I Nystrom S Konradsson P Herland A Inganas O Stabo-Eeg F Lindgren M Westermark GT Lannfelt L Nilsson LN Hammarstrom P Imaging distinct conformational states of amyloid-beta fibrils in Alzheimer’s disease using novel luminescent probes ACS Chem Biol 2007 2 553 560 17672509
  69. [78]Petkova AT Leapman RD Guo Z Yau WM Mattson MP Tycko R Self-propagating, molecular-level polymorphism in Alzheimer’s beta-amyloid fibrils Science 2005 307 262 265 15653506
  70. [79]Ray S Britschgi M Herbert C Takeda-Uchimura Y Boxer A Blennow K Friedman LF Galasko DR Jutel M Karydas A Kaye JA Leszek J Miller BL Minthon L Quinn JF Rabinovici GD Robinson WH Sabbagh MN So YT Sparks DL Tabaton M Tinklenberg J Yesavage JA Tibshirani R Wyss-Coray T Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins Nat Med 2007 13 1359 1362 17934472
  71. [80]Paravastu AK Qahwash I Leapman RD Meredith SC Tycko R Seeded growth of {beta}-amyloid fibrils from Alzheimer’s brain-derived fibrils produces a distinct fibril structure Proc Natl Acad Sci U S A 2009 PMC2678625 19376973
  72. [81]Wang Y Klunk WE Debnath ML Huang GF Holt DP Shao L Mathis CA Development of a PET/SPECT agent for amyloid imaging in Alzheimer’s disease J Mol Neurosci 2004 24 55 62 15314250
  73. [82]Klunk WE Engler H Nordberg A Wang Y Blomqvist G Holt DP Bergstrom M Savitcheva I Huang GF Estrada S Ausen B Debnath ML Barletta J Price JC Sandell J Lopresti BJ Wall A Koivisto P Antoni G Mathis CA Langstrom B Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B Ann Neurol 2004 55 306 319 14991808
  74. [83]Grimmer T Henriksen G Wester HJ Forstl H Klunk WE Mathis CA Kurz A Drzezga A Clinical severity of Alzheimer’s disease is associated with PIB uptake in PET Neurobiol Aging 2008 18346821
  75. [84]Klunk WE Lopresti BJ Ikonomovic MD Lefterov IM Koldamova RP Abrahamson EE Debnath ML Holt DP Huang GF Shao L DeKosky ST Price JC Mathis CA Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer’s disease brain but not in transgenic mouse brain J Neurosci 2005 25 10598 10606 16291932 PMC6725842
  76. [85]Rosen RF Walker LC LeVine H 3rd Binding in Aged Primate Brain: Unique Enrichment of High Affinity Sites in Humans with AD Neurobiol Aging 2009 in press
  77. [88]Kane MD Lipinski WJ Callahan MJ Bian F Durham RA Schwarz RD Roher AE Walker LC Evidence for seeding of beta -amyloid by intracerebral infusion of Alzheimer brain extracts in beta -amyloid precursor protein-transgenic mice J Neurosci 2000 20 3606 3611 10804202 PMC6772682
  78. [89]Walker LC Bian F Callahan MJ Lipinski WJ Durham RA LeVine H Modeling Alzheimer’s disease and other proteopathies in vivo: is seeding the key? Amino Acids 2002 23 87 93 12373522
  79. [90]Deshpande A Mina E Glabe C Busciglio J Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons J Neurosci 2006 26 6011 6018 16738244 PMC6675207
  80. [91]Koffie RM Meyer-Luehmann M Hashimoto T Adams KW Mielke ML Garcia-Alloza M Micheva KD Smith SJ Kim ML Lee VM Hyman BT Spires-Jones TL Oligomeric amyloid {beta} associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques Proc Natl Acad Sci U S A 2009 PMC2656196 19228947
  81. [92]Bitan G Kirkitadze MD Lomakin A Vollers SS Benedek GB Teplow DB Amyloid beta-protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways Proc Natl Acad Sci U S A 2003 100 330 335 12506200 PMC140968
  82. [93]Duering M Grimm MO Grimm HS Schroder J Hartmann T Mean age of onset in familial Alzheimer’s disease is determined by amyloid beta 42 Neurobiol Aging 2005 26 785 788 15718035
  83. [94]Bitan G Vollers SS Teplow DB Elucidation of primary structure elements controlling early amyloid beta-protein oligomerization J Biol Chem 2003 278 34882 34889 12840029
  84. [96]Shankar GM Li S Mehta TH Garcia-Munoz A Shepardson NE Smith I Brett FM Farrell MA Rowan MJ Lemere CA Regan CM Walsh DM Sabatini BL Selkoe DJ Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory Nat Med 2008 14 837 842 18568035 PMC2772133
  85. [97]Glabe CG Structural classification of toxic amyloid oligomers J Biol Chem 2008 283 29639 29643 18723507 PMC2573087
  86. [98]Kayed R Sokolov Y Edmonds B McIntire TM Milton SC Hall JE Glabe CG Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein misfolding diseases J Biol Chem 2004 279 46363 46366 15385542
  87. [99]Sokolov Y Kozak JA Kayed R Chanturiya A Glabe C Hall JE Soluble amyloid oligomers increase bilayer conductance by altering dielectric structure J Gen Physiol 2006 128 637 647 17101816 PMC2151594
  88. [100]Georganopoulou DG Chang L Nam JM Thaxton CS Mufson EJ Klein WL Mirkin CA Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease Proc Natl Acad Sci U S A 2005 102 2273 2276 15695586 PMC548981
  89. [101]Necula M Kayed R Milton S Glabe CG Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct J Biol Chem 2007 282 10311 10324 17284452
  90. [102]Esler WP Stimson ER Jennings JM Vinters HV Ghilardi JR Lee JP Mantyh PW Maggio JE Alzheimer’s disease amyloid propagation by a template-dependent dock-lock mechanism Biochemistry 2000 39 6288 6295 10828941
  91. [103]O’Nuallain B Williams AD Westermark P Wetzel R Seeding specificity in amyloid growth induced by heterologous fibrils J Biol Chem 2004 279 17490 17499 14752113
  92. [105]Robbins EM Betensky RA Domnitz SB Purcell SM Garcia-Alloza M Greenberg C Rebeck GW Hyman BT Greenberg SM Frosch MP Bacskai BJ Kinetics of cerebral amyloid angiopathy progression in a transgenic mouse model of Alzheimer disease J Neurosci 2006 26 365 371 16407531 PMC6674403
  93. [106]Lemere CA Maier M Jiang L Peng Y Seabrook TJ Amyloid-beta immunotherapy for the prevention and treatment of Alzheimer disease: lessons from mice, monkeys, and humans Rejuvenation Res 2006 9 77 84 16608400
  94. [109]Martin LJ Sisodia SS Koo EH Cork LC Dellovade TL Weidemann A Beyreuther K Masters C Price DL Amyloid precursor protein in aged nonhuman primates Proc Natl Acad Sci U S A 1991 88 1461 1465 1899927 PMC51038
  95. [110]Rosen RF Farberg AS Gearing M Dooyema J Long PM Anderson DC Davis-Turak J Coppola G Geschwind DH Pare JF Duong TQ Hopkins WD Preuss TM Walker LC Tauopathy with paired helical filaments in an aged chimpanzee J Comp Neurol 2008 509 259 270 18481275 PMC2573460
  96. [111]Satou T Cummings BJ Head E Nielson KA Hahn FF Milgram NW Velazquez P Cribbs DH Tenner AJ Cotman CW The progression of beta-amyloid deposition in the frontal cortex of the aged canine Brain Res 1997 774 35 43 9452189
  97. [112]Cummings BJ Head E Afagh AJ Milgram NW Cotman CW Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine Neurobiol Learning Memory 1996 66 11 23 8661247
  98. [113]Cummings BJ Satou T Head E Milgram NW Cole GM Savage MJ Podlisny MB Selkoe DJ Siman R Greenberg BD Cotman CW Diffuse plaques contain C-terminal A beta 42 and not A beta 40: evidence from cats and dogs Neurobiol Aging 1996 17 653 659 8832640
  99. [114]Head E Pop V Vasilevko V Hill M Saing T Sarsoza F Nistor M Christie LA Milton S Glabe C Barrett E Cribbs D A two-year study with fibrillar beta-amyloid (Abeta) immunization in aged canines: effects on cognitive function and brain Abeta J Neurosci 2008 28 3555 3566 18385314 PMC6671080
  100. [115]Games D Buttini M Kobayashi D Schenk D Seubert P Mice as models: transgenic approaches and Alzheimer’s disease J Alzheimers Dis 2006 9 133 149 16914852
  101. [116]McGowan E Eriksen J Hutton M A decade of modeling Alzheimer’s disease in transgenic mice Trends Genet 2006 22 281 289 16567017
  102. [117]LeVine H Walker LC Conn MP Model’s of Alzheimer’s Disease Handbook of Models for Human Aging 2006 121 134 Academic Press / Elsevier New York
  103. [119]Flood DG Reaume AG Dorfman KS Lin YG Lang DM Trusko SP Savage MJ Annaert WG De Strooper B Siman R Scott RW FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproduction Neurobiol Aging 2002 23 335 348 11959395
  104. [120]Fung J Frost D Chakrabartty A McLaurin J Interaction of human and mouse Abeta peptides J Neurochem 2004 91 1398 1403 15584916
  105. [122]Ye L Morgenstern JL Lamb JR Lockhart A Characterisation of the binding of amyloid imaging tracers to rodent Abeta fibrils and rodent-human Abeta co-polymers Biochem Biophys Res Commun 2006 347 669 677 16842745
  106. [123]McGowan E Pickford F Kim J Onstead L Eriksen J Yu C Skipper L Murphy MP Beard J Das P Jansen K Delucia M Lin WL Dolios G Wang R Eckman CB Dickson DW Hutton M Hardy J Golde T Abeta42 is essential for parenchymal and vascular amyloid deposition in mice Neuron 2005 47 191 199 16039562 PMC1373682
  107. [124]Gotz J Chen F van Dorpe J Nitsch RM Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils Science 2001 293 1491 1495 11520988
  108. [125]Lewis J Dickson DW Lin WL Chisholm L Corral A Jones G Yen SH Sahara N Skipper L Yager D Eckman C Hardy J Hutton M McGowan E Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP Science 2001 293 1487 1491 11520987
  109. [128]Kalback W Watson MD Kokjohn TA Kuo YM Weiss N Luehrs DC Lopez J Brune D Sisodia SS Staufenbiel M Emmerling M Roher AE APP transgenic mice Tg2576 accumulate Abeta peptides that are distinct from the chemically modified and insoluble peptides deposited in Alzheimer’s disease senile plaques Biochemistry 2002 41 922 928 11790115
  110. [129]Ye L Morgenstern JL Gee AD Hong G Brown J Lockhart A Delineation of positron emission tomography imaging agent binding sites on beta-amyloid peptide fibrils J Biol Chem 2005 280 23599 23604 15855161
  111. [130]LeVine H 3rd Multiple ligand binding sites on A beta(1-40) fibrils Amyloid 2005 12 5 14 16076606

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Authors
Murphy, M. P., & LeVine, H.
Affiliations
University of Kentucky (US)
Corresponding author
  • Murphy, M. Paul
  • LeVine, Harry
Venue
Journal of Alzheimer's Disease
Publisher
SAGE Publications
Published
2010-01-06
Volume
19
Issue
1
Pages
311-323
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-2010-1221
PMC
PMC2813509
OpenAlex
W1605885548
Cited by
1,750
References
21
Citations by year
2026: 87 · 2025: 160 · 2024: 220 · 2023: 218 · 2022: 229 · 2021: 227 · 2020: 181 · 2019: 119 · 2018: 122 · 2017: 64 · 2016: 41 · 2015: 25 · 2014: 17 · 2013: 8 · 2012: 15
FWCI
8.45
Type
journal article
Language
en
Open access
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (P01AG005119, AG-005119)
  • National Institute of Neurological Disorders and Stroke (R01NS058382, NS-058382)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid-beta
MeSH terms
Alzheimer Disease, Animals, Brain, Humans, Peptide Fragments, Polymorphism, Genetic, Protein Conformation, Amyloid beta-Peptides

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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