Intraneuronal Alzheimer Aβ42 accumulates in multivesicular bodies and is associated with synaptic pathology

American Journal of Pathology

Volumn 161, Issue 5, 2002, Pages 1869-1879

  Takahashi, Reisuke H ^a,b   Milner, Teresa A ^a   Li, Feng ^a   Nam, Ellen E ^a   Edgar, Mark A ^a   Yamaguchi, Haruyasu ^c   Beal, M Flint ^a   Xu, Huaxi ^b   Greengard, Paul ^b   Gouras, Gunnar K ^a,b  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

^c GUNMA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN (1 42); AMYLOID BETA-PROTEIN (1-42); AMYLOID PRECURSOR PROTEIN; PEPTIDE FRAGMENT;

AGING; ALZHEIMER DISEASE; ANIMAL; ARTICLE; BRAIN; CHEMISTRY; CYTOLOGY; CYTOPLASM VESICLE; GENETICS; HUMAN; IMMUNOELECTRON MICROSCOPY; IMMUNOLOGY; METABOLISM; MIDDLE AGED; MOUSE; MOUSE MUTANT; NERVE CELL; PATHOLOGY; RAT; SYNAPSE; TRANSGENIC MOUSE; ULTRASTRUCTURE; AGE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; BRAIN DYSFUNCTION; CELL VACUOLE; CONTROLLED STUDY; DISEASE MODEL; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN LOCALIZATION;

AGING; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BRAIN; CYTOPLASMIC VESICLES; HUMANS; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; MICROSCOPY, IMMUNOELECTRON; MIDDLE AGED; NEURONS; PEPTIDE FRAGMENTS; RATS; SYNAPSES;

EID: 0036827031     PISSN: 00029440     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0002-9440(10)64463-X     Document Type: Article

References (65)

1. Selkoe DJ: Alzheimer's disease: Genes, proteins, and therapy. Physiol Rev 2001, 81:741-766
2. Gouras GK, Tsai J, Naslund J, Vincent B, Edgar M, Checler F, Greenfield JP, Haroutunian V, Buxbaum JD, Xu H, Greengard P, Relkin NR: Intraneuronal Abeta42 accumulation in human brain. Am J Pathol 2000, 156:15-20
3. Wilson CA, Doms RW, Lee VM: Intracellular APP processing and A beta production in Alzheimer disease. J Neuropathol Exp Neurol 1999, 58:787-794
4. Hartmann T: Intracellular biology of Alzheimer's disease amyloid beta peptide Eur Arch Psychiatry Clin Neurosci 1999, 249:291-298
5. Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, Jantzen P, Wright K, Saad I, Mueller R, Morgan D, Sanders S, Zehr C, O'Campo K, Hardy J, Prada CM, Eckman C, Younkin S, Hsiao K, Duff K: Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med 1998, 4:97-100
6. Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, Younkin L, Good MA, Bliss TV, Hyman BT, Younkin SG, Hsiao KK: Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 1999, 2:271-276
7. Moechars D, Dewachter I, Lorent K, Reverse D, Baekelandt V, Naidu A, Tesseur I, Spittaels K, Haute CV, Checler F, Godaux E, Cordell B, Van Leuven F: Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J Biol Chem 1999, 274:6483-6492
8. Kawarabayashi T, Younkin LH, Saido TC, Shoji M, Ashe KH, Younkin SG: Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J Neurosci 2001, 21:372-381
9. Pratico D, Uryu K, Leight S, Trojanoswki JQ, Lee VM: Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 2001, 21:4183-4187
10. Koo EH, Squazzo SL: Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J Biol Chem 1994, 269:17386-17389
11. Perez RG, Soriano S, Hayes JD, Ostaszewski B, Xia W, Selkoe DJ, Chen X, Stokin GB, Koo EH: Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta 42. J Biol Chem 1999, 274:18851-18856
12. Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L: Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci USA 1999, 96:3228-3233
13. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G: Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996, 274:99-102
14. Irizarry MC, McNamara M, Fedorchak K, Hsiao K, Hyman BT: APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1. J Neuropathol Exp Neurol 1997, 56:965-973
15. Teller JK, Russo C, DeBusk LM, Angelini G, Zaccheo D, Dagna-Bricarelli F, Scartezzini P, Bertolini S, Mann DM, Tabaton M, Gambetti P: Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in Down's syndrome. Nat Med 1996, 2:93-95
16. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL: Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 1999, 46:860-866
17. Walsh DM, Tseng BP, Rydel RE, Podlisny MB, Selkoe DJ: The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain. Biochemistry 2000, 39:10831-10839
18. Skovronsky DM, Doms RW, Lee VM: Detection of a novel intraneuronal pool of insoluble amyloid beta protein that accumulates with time in culture. J Cell Biol 1998, 141:1031-1039
19. Chui DH, Tanahashi H, Ozawa K, Ikeda S, Checler F, Ueda O, Suzuki H, Araki W, Inoue H, Shirotani K, Takahashi K, Gallyas F, Tabira T: Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nat Med 1999, 5:560-564
20. Askanas V, Engel WK: Inclusion-body myositis: Newest concepts of pathogenesis and relation to aging and Alzheimer disease. J Neuropathol Exp Neurol 2001, 60:1-14
21. Ginsberg SD, Galvin JE, Lee VM, Rorke LB, Dickson DW, Wolfe JH, Jones MZ, Trojanowski JQ: Accumulation of intracellular amyloidbeta peptide (A beta 1-40)in mucopolysaccharidosis brains. J Neuropathol Exp Neurol 1999, 58:815-824
22. D'Andrea MR, Nagele RG, Wang HY, Peterson PA, Lee DH: Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer's disease. Histopathology 2001, 38:120-134
23. Gyure KA, Durham R, Stewart WF, Smialek JE, Troncoso JC: Intraneuronal Abeta-amyloid precedes development of amyloid plaques in Down syndrome. Arch Pathol Lab Med 2001, 125:489-492
24. Mochizuki A, Tamaoka A, Shimohata A, Komatsuzaki Y, Shoji S: Abeta42-positive non-pyramidal neurons around amyloid plaques in Alzheimer's disease. Lancet 2000, 355:42-43
25. Wirths O, Multhaup G, Czech C, Blanchard V, Moussaoui S, Tremp G, Pradier L, Beyreuther K, Bayer TA: Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice. Neurosci Lett 2001, 306:116-120
26. Busciglio J, Pelsman A, Wong C, Pigino G, Yuan ML, Mori H. Yankner BA: Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron 2002, 33:677-688
27. Yamaguchi H, Maat-Schieman ML, van Duinen SG, Prins FA, Neeskens P, Natte R, Roos RA: Amyloid beta protein (Abeta) starts to deposit as plasma membrane-bound form in diffuse plaques of brains from hereditary cerebral hemorrhage with amyloidosis-Dutch type, Alzheimer disease and nondemented aged subjects. J Neuropathol Exp Neurol 2000, 59:723-732
28. Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, Greengard P, Xu H: Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci 2001, 21:2561-2570
29. Buxbaum JD, Gandy SE, Cicchetti P, Ehrlich ME, Czernik AJ, Fracasso RP, Ramabhadran TV, Unterbeck AJ, Greengard P: Processing of Alzheimer beta/A4 amyloid precursor protein: Modulation by agents that regulate protein phosphorylation. Proc Natl Acad Sci USA 1990, 87:6003-6006
30. Milner TA, Lee A, Aicher SA, Rosin DL: Hippocampal alpha2a-adrenergic receptors are located predominantly presynaptically but are also found postsynaptically and in selective astrocytes. J Comp Neurol 1998, 395:310-327
31. Chan J, Aoki C, Pickel VM: Optimization of differential immunogold-silver and peroxidase labeling with maintenance of ultrastructure in brain sections before plastic embedding. J Neurosci Methods 1990, 33:113-127
32. Peters A, Palay SL, Webster HD: The Fine Structure of the Nervous System. Oxford, Oxford University Press, 1991
33. Leranth C, Pickel VM: Neuroanatomical Tract Tracing Methods 2 New York, Plenum, 1989, pp 120-170
34. Caporaso GL, Takei K, Gandy SE, Matteoli M, Mundigl O, Greengard P, De Camilli P: Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer beta/A4 amyloid precursor protein. J Neurosci 1994, 14:3122-3138
35. Hartmann T, Bieger SC, Bruhl B, Tienari PJ, Ida N, Allsop D, Roberts GW, Masters CL, Dotti CG, Unsicker K, Beyreuther K: Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides. Nat Med 1997, 3:1016-1020
36. Zheng H, Jiang M, Trumbauer ME, Sirinathsinghji DJ, Hopkins R, Smith DW, Heavens RP, Dawson GR, Boyce S, Conner MW: Beta-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 1995, 81:525-531
37. Perry G, Siedlak S, Mulvihill P, Kancherla M, Mijares M, Kawai M, Gambetti P, Sharma S, Maggiora L, Cornette J: Immunolocalization of the amyloid precursor protein within the senile plaque. Prog Clin Biol Res 1989, 317:1021-1025
38. Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D: Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease J Neurosci 1996, 16:5795-5811
39. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R: Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991, 30:572-580
40. Perez RG, Zheng H, Van der Ploeg LH, Koo EH: The beta-amyloid precursor protein of Alzheimer's disease enhances neuron viability and modulates neuronal polarity J Neurosci 1997, 17:9407-9414
41. Seabrook GR, Smith DW, Bowery BJ, Easter A, Reynolds T, Fitzjohn SM, Morton RA, Zheng H, Dawson GR, Sirinathsinghji DJS: Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. Neuropharmacology 1999, 38:349-359
42. 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
43. 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
44. Gouras GK, Xu H, Jovanovic JN, Buxbaum JD, Wang R, Greengard P, Relkin NR, Gandy S: Generation and regulation of beta-amyloid peptide variants by neurons. J Neurochem 1998, 71:1920-1925
45. 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
46. Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ: Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: Implications for initial events in amyloid plaque formation. Neurobiol Dis 1996, 3:16-32
47. Gruenberg J, Maxfield FR: Membrane transport in the endocytic pathway. Curr Opin Cell Biol 1995, 7:552-563
48. Katzmann DJ, Babst M, Emr SD: Ubiquitin-Dependent Sorting Into the Multivesicular Body Pathway Requires the Function of a Conserved Endosomal Protein Sorting Complex, ESCRT-I Cell 2001, 106:145-155
49. Nixon RA, Cataldo AM, Mathews PM: The endosomal-lysosomal system of neurons in Alzheimer's disease pathogenesis: A review. Neurochem Res 2000, 25:1161-1172
50. Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA: Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: Differential effects of APOE genotype and presenilin mutations Am J Pathol 2000, 157:277-286
51. Yamazaki T, Chang TY, Haass C, Ihara Y: Accumulation and aggregation of amyloid (beta)-protein in late endosomes of Niemann-Pick type C cells. J Biol Chem 2000, 276:4454-4460
52. Runz H, Rietdorf J, Tomic I, de Bernard M, Beyreuther K, Pepperkok R, Hartmann T: Inhibition of intracellular cholesterol transport alters presenilin localization and amyloid precursor protein processing in neuronal cells. J Neurosci 2002, 22: 1679-1689
53. Yang AJ, Chandswangbhuvana D, Margol L, Glabe CG: Loss of endosomal/lysosomal membrane impermeability is an early event in amyloid Abeta1-42 pathogenesis. J Neurosci Res 1998, 52:691-698
54. Zhang Y, McLaughlin R, Goodyer C, LeBlanc A: Selective cytotoxicity of intracellular amyloid (beta) peptidel-42 through p53 and Bax in cultured primary human neurons. J Cell Biol 2002, 156:519-529
55. Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS: Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP Nature 2001, 414:643-648
56. Sisodia SS: Biomedicine: A cargo receptor mystery APParently solved? Science 2002, 295:805-807
57. Saito N, Okada Y, Noda Y, Kinoshita Y, Kondo S, Hirokawa N: KIFC2 is a novel neuron-specific C-terminal type kinesin superfamily motor for dendritic transport of multivesicular body-like organelles. Neuron 1997, 18:425-438
58. Trojanowski JQ, Lee VM: "Fatal attractions" of proteins. A comprehensive hypothetical mechanism underlying Alzheimer's disease and other neurodegenerative disorders. Ann NY Acad Sci 2000, 924: 62-67
59. Wild-Bode C, Yamazaki T, Capell A, Leimer U, Steiner H, Ihara Y, Haass C: Intracellular generation and accumulation of amyloid beta-peptide terminating at amino acid 42. J Biol Chem 1997, 272:16085-16088
60. Martin BL, Schrader-Fischer G, Busciglio J, Duke M, Paganetti P, Yankner BA: Intracellular accumulation of beta-amyloid in cells expressing the Swedish mutant amyloid precursor protein. J Biol Chem 1995, 270:26727-26730
61. Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Stenh C, Luthman J, Teplow DB, Younkin SG, Naslund J, Lannfelt L: The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat Neurosci 2001, 4:887-893
62. Bahr BA, Hoffman KB, Yang AJ, Hess US, Glabe CG, Lynch G: Amyloid beta protein is internalized selectively by hippocampal field CA1 and causes neurons to accumulate amyloidogenic carboxyterminal fragments of the amyloid precursor protein. J Comp Neurol 1998, 397:139-147
63. Longva KE, Blystad FD, Stang E, Larsen AM, Johannessen LE, Madshus IH: Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies. J Cell Biol 2002, 156:843-854
64. Koo EH, Sisodia SS, Archer DR, Martin LJ, Weidemann A, Beyreuther K, Fischer P, Masters CL, Price DL: Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci USA 1990, 87:1561-1565
65. Tienari PJ, De Strooper B, Ikonen E, Simons M, Weidemann A, Czech C, Hartmann T, Ida N, Multhaup G, Masters CL, Van Leuven F, Beyreuther K, Dotti CG: The beta-amyloid domain is essential for axonal sorting of amyloid precursor protein. EMBO J 1996, 15:5218-5229