Alzheimer brain-derived amyloid β-protein impairs synaptic remodeling and memory consolidation

Neurobiology of Aging

Volumn 34, Issue 5, 2013, Pages 1315-1327

  Borlikova, Gilyana G ^a   Trejo, Margarita ^b,c   Mably, Alexandra J ^a   Mc Donald, Jessica M ^a   Sala Frigerio, Carlo ^a   Regan, Ciaran M ^a   Murphy, Keith J ^a   Masliah, Eliezer ^b,c   Walsh, Dominic M ^a  

^a UNIVERSITY COLLEGE DUBLIN   (Ireland)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Alzheimer's disease; Amyloid protein; Episodic memory; Intracerebroventricular injection; Memory associated synaptic reorganization; Non fibrillar water soluble A ; Passive avoidance; Synaptic plasticity

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR LIKE PROTEIN 1; AMYLOID PRECURSOR LIKE PROTEIN 2; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE 1; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; PRION PROTEIN; TAU PROTEIN; UNCLASSIFIED DRUG;

AGED; ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DENTATE GYRUS; FEMALE; HIPPOCAMPAL CA1 REGION; HUMAN; HUMAN TISSUE; LONG TERM MEMORY; MALE; MEMORY CONSOLIDATION; MEMORY DISORDER; MOLECULAR PATHOLOGY; NERVE CELL PLASTICITY; NONHUMAN; PASSIVE AVOIDANCE; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; RAT; SYNAPTIC INHIBITION; SYNAPTIC TRANSMISSION;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; AVOIDANCE LEARNING; BRAIN; FEMALE; HUMANS; MALE; MEMORY, EPISODIC; NEURONAL PLASTICITY; RATS; RATS, WISTAR; SYNAPTIC TRANSMISSION;

EID: 84873468886     PISSN: 01974580     EISSN: 15581497     Source Type: Journal    
DOI: 10.1016/j.neurobiolaging.2012.10.028     Document Type: Article

References (92)

1. Alexinsky T., Przybyslawski J., Mileusnic R., Rose S.P., Sara S.J. Antibody to day-old chick brain glycoprotein produces amnesia in adult rats. Neurobiol. Learn. Mem. 1997, 67:14-20.
2. Alzheimer's Association, 2011. Generation Alzheimer's: the Defining Disease of the Baby Boomers. Alzheimer's Association, Chicago, IL.
3. Ansari M.A., Roberts K.N., Scheff S.W. Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury. Free Radical Biol. Med. 2008, 45:443-452.
4. Applegate M.D., Landfield P.W. Synaptic vesicle redistribution during hippocampal frequency potentiation and depression in young and aged rats. J. Neurosci. 1988, 8:1096-1111.
5. Avila J., Lucas J.J., Perez M., Hernandez F. Role of tau protein in both physiological and pathological conditions. Physiol. Rev. 2004, 84:361-384.
6. Barry A.E., Klyubin I., Mc Donald J.M., Mably A.J., Farrell M.A., Scott M., Walsh D.M., Rowan M.J. Alzheimer's Disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J. Neurosci. 2011, 31:7259-7263.
7. Boland B., Smith D.A., Mooney D., Jung S.S., Walsh D.M., Platt F.M. Macroautophagy is not directly involved in the metabolism of amyloid precursor protein. J. Biol. Chem. 2010, 285:37415-37426.
8. Buttini M., Masliah E., Barbour R., Grajeda H., Motter R., Johnson-Wood K., Khan K., Seubert P., Freedman S., Schenk D., Games D. β-Amyloid immunotherapy prevents synaptic degeneration in a mouse model of Alzheimer's disease. J. Neurosci. 2005, 25:9096-9101.
9. Cirrito J.R., May P.C., O'Dell M.A., Taylor J.W., Parsadanian M., Cramer J.W., Audia J.E., Nissen J.S., Bales K.R., Paul S.M., DeMattos R.B., Holtzman D.M. In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J. Neurosci. 2003, 23:8844-8853.
10. Cleary J.P., Walsh D.M., Hofmeister J.J., Shankar G.M., Kuskowski M.A., Selkoe D.J., Ashe K.H. Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat. Neurosci. 2005, 8:79-84.
11. Coleman P.D., Yao P.J. Synaptic slaughter in Alzheimer's disease. Neurobiol. Aging 2003, 24:1023-1027.
12. Conboy L., Murphy K.J., Regan C.M. Amyloid precursor protein expression in the rat hippocampal dentate gyrus modulates during memory consolidation. J. Neurochem. 2005, 95:1677-1688.
13. Davies C.A., Mann D.M., Sumpter P.Q., Yates P.O. A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease. J. Neurol. Sci. 1987, 78:151-164.
14. Davis H.P., Squire L.R. Protein synthesis and memory: a review. Psychol. Bull. 1984, 96:518-559.
15. Deller T., Bas Orth C., Del Turco D., Vlachos A., Burbach G.J., Drakew A., Chabanis S., Korte M., Schwegler H., Haas C.A., Frotscher M. A role for synaptopodin and the spine apparatus in hippocampal synaptic plasticity. Ann. Anat. 2007, 189:5-16.
16. Dere E., De Souza-Silva M.A., Frisch C., Teubner B., Söhl G., Willecke K., Huston J.P. Connexin30-deficient mice show increased emotionality and decreased rearing activity in the open-field along with neurochemical changes. Eur. J. Neurosci. 2003, 18:629-638.
17. De Strooper B. Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process. Physiol. Rev. 2010, 90:465-494.
18. Doyle E., Nolan P.M., Bell R., Regan C.M. Intraventricular infusions of anti-neural cell adhesion molecules in a discrete posttraining period impair consolidation of a passive avoidance response in the rat. J. Neurochem. 1992, 59:1570-1573.
19. Ehrlich I., Klein M., Rumpel S., Malinow R. PSD-95 is required for activity-driven synapse stabilization. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:4176-4181.
20. Eyre M.D., Richter-Levin G., Avital A., Stewart M.G. Morphological changes in hippocampal dentate gyrus synapses following spatial learning in rats are transient. Eur. J. Neurosci. 2003, 17:1973-1980.
21. Ferri C.P., Prince M., Brayne C., Brodaty H., Fratiglioni L., Ganguli M., Hall K., Hasegawa K., Hendrie H., Huang Y., Jorm A., Mathers C., Menezes P.R., Rimmer E., Scazufca M. Global prevalence of dementia: a Delphi consensus study. Lancet 2005, 366:2112-2117.
22. Foley A.G., Hartz B.P., Gallagher H.C., Ronn L.C., Berezin V., Bock E., Regan C.M. A synthetic peptide ligand of neural cell adhesion molecule (NCAM) IgI domain prevents NCAM internalization and disrupts passive avoidance learning. J. Neurochem. 2000, 74:2607-2613.
23. Freir D.B., Fedriani R., Scully D., Smith I.M., Selkoe D.J., Walsh D.M., Regan C.M. Aβ oligomers inhibit synapse remodelling necessary for memory consolidation. Neurobiol. Aging 2011, 32:2211-2218.
24. Freir D.B., Nicoll A.J., Klyubin I., Panico S., Mc Donald J.M., Risse E., Asante E.A., Farrow M.A., Sessions R.B., Saibil H.R., Clarke A.R., Rowan M.J., Walsh D.M., Collinge J. Interaction between prion protein and toxic amyloid [beta] assemblies can be therapeutically targeted at multiple sites. Nat. Commun. 2011, 2:336.
25. Games D., Buttini M., Kobayashi D., Schenk D., Seubert P. Mice as models: transgenic approaches and Alzheimer's disease. J. Alzheimers Dis. 2006, 9(3 suppl):133-149.
26. Gonatas N.K., Anderson W., Evangelista I. The contribution of altered synapses in the senile plaque: an electron microscopic study in Alzheimer's dementia. J. Neuropathol. Exp. Neurol. 1967, 26:25-39.
27. Gray B.C., Siskova Z., Perry V.H., O'Connor V. Selective presynaptic degeneration in the synaptopathy associated with ME7-induced hippocampal pathology. Neurobiol. Dis. 2009, 35:63-74.
28. Grober E., Hall C.B., Lipton R.B., Zonderman A.B., Resnick S.M., Kawas C. Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's disease. J. Int. Neuropsychol. Soc. 2008, 14:266-278.
29. Gunther E.C., Strittmatter S.M. Beta-amyloid oligomers and cellular prion protein in Alzheimer's disease. J. Mol. Med. (Berl.) 2010, 88:331-338.
30. Hering H., Sheng M. Dentritic spines: structure, dynamics and regulation. Nat. Rev. Neurosci. 2001, 2:880-888.
31. Jan A., Hartley D.M., Lashuel H.A. Preparation and characterization of toxic Abeta aggregates for structural and functional studies in Alzheimer's disease research. Nat. Protoc. 2010, 5:1186-1209.
32. Jedlicka P., Vlachos A., Schwarzacher S.W., Deller T. A role for the spine apparatus in LTP and spatial learning. Behav. Brain Res. 2008, 192:12-19.
33. Kandel E.R. The molecular biology of memory storage: a dialog between genes and synapses. Biosci. Rep. 2001, 21:565-611.
34. Klein W.L., Krafft G.A., Finch C.E. Targeting small Aβ oligomers: the solution to an Alzheimer's disease conundrum?. Trends Neurosci. 2001, 24:219-224.
35. Klyubin I., Betts V., Welzel A.T., Blennow K., Zetterberg H., Wallin A., Lemere C.A., Cullen W.K., Peng Y., Wisniewski T., Selkoe D.J., Anwyl R., Walsh D.M., Rowan M.J. Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization. J. Neurosci. 2008, 28:4231-4237.
36. Knaus P., Betz H., Rehm H. Expression of synaptophysin during postnatal development of the mouse brain. J. Neurochem. 1986, 47:1302-1304.
37. Kowall N.W., Kosik K.S. Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease. Ann. Neurol. 1987, 22:639-643.
38. Kuo Y.M., Emmerling M.R., Vigo-Pelfrey C., Kasunic T.C., Kirkpatrick J.B., Murdoch G.H., Ball M.J., Roher A.E. Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. J. Biol. Chem. 1996, 271:4077-4081.
39. Lambert M.P., Barlow A.K., Chromy B.A., Edwards C., Freed R., Liosatos M., Morgan T.E., Rozovsky I., Trommer B., Viola K.L., Wals P., Zhang C., Finch C.E., Krafft G.A., Klein W.L. Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:6448-6453.
40. Lamprecht R., LeDoux J. Structural plasticity and memory. Nat. Rev. Neurosci. 2004, 5:45-54.
41. Lauren J., Gimbel D.A., Nygaard H.B., Gilbert J.W., Strittmatter S.M. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-[bgr] oligomers. Nature 2009, 457:1128-1132.
42. Lechner H.A., Squire L.R., Byrne J.H. 100 years of consolidation-remembering Muller and Pilzecker. Learn. Mem. 1999, 6:77-87.
43. Lesne S., Koh M.T., Kotilinek L., Kayed R., Glabe C.G., Yang A., Gallagher M., Ashe K.H. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2006, 440:352-357.
44. Li S., Hong S., Shepardson N.E., Walsh D.M., Shankar G.M., Selkoe D. Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 2009, 62:788-801.
45. Lin Y., Jover-Mengual T., Wong J., Bennett M.V.L., Zukin R.S. PSD-95 and PKC converge in regulating NMDA receptor trafficking and gating. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:19902-19907.
46. Lue L.F., Kuo Y.M., Roher A.E., Brachova L., Shen Y., Sue L., Beach T., Kurth J.H., Rydel R.E., Rogers J. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am. J. Pathol. 1999, 155:853-862.
47. Marrone D.F. Ultrastructural plasticity associated with hippocampal-dependent learning: a meta-analysis. Neurobiol. Learn. Mem. 2007, 87:361-371.
48. Masliah E., Mallory M., Alford M., DeTeresa R., Hansen L.A., McKeel D.W., Morris J.C. Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurology 2001, 56:127-129.
49. Masliah E., Terry R.D., DeTeresa R.M., Hansen L.A. Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer disease. Neurosci. Lett. 1989, 103:234-239.
50. McDonald J.M., Cairns N.J., Taylor-Reinwald L., Holtzman D., Walsh D.M. The levels of water-soluble and triton-soluble Aβ are increased in Alzheimer's disease brain. Brain Res. 2012, 1450:138-147.
51. Mc Donald J.M., Savva G.M., Brayne C., Welzel A.T., Forster G., Shankar G.M., Selkoe D.J., Ince P.G., Walsh D.M. The presence of sodium dodecyl sulphate-stable Aβ dimers is strongly associated with Alzheimer-type dementia. Brain 2010, 133:1328-1341.
52. McLean C.A., Cherny R.A., Fraser F.W., Fuller S.J., Smith M.J., Beyreuther K., Bush A.I., Masters C.L. Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann. Neurol. 1999, 46:860-866.
53. Mesulam M.M. Neuroplasticity failure in Alzheimer's disease: bridging the gap between plaques and tangles. Neuron 1999, 24:521-529.
54. Monopoli M.P., Raghnaill M.N., Loscher J.S., O'Sullivan N.C., Pangalos M.N., Ring R.H., von Schack D., Dunn M.J., Regan C.M., Pennington S., Murphy K.J. Temporal proteomic profile of memory consolidation in the rat hippocampal dentate gyrus. Proteomics 2011, 11:4189-4201.
55. Mormino E.C., Kluth J.T., Madison C.M., Rabinovici G.D., Baker S.L., Miller B.L., Koeppe R.A., Mathis C.A., Weiner M.W., Jagust W.J. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain 2009, 132:1310-1323.
56. Murphy K.J., Regan C.M. Contributions of cell adhesion molecules to altered synaptic weightings during memory consolidation. Neurobiol. Learn. Mem. 1998, 70:73-81.
57. Nakamura S., Murayama N., Noshita T., Annoura H., Ohno T. Progressive brain dysfunction following intracerebroventricular infusion of beta(1-42)-amyloid peptide. Brain Res. 2001, 912:128-136.
58. O'Malley A., O'Connell C., Regan C.M. Ultrastructural analysis reveals avoidance conditioning to induce a transient increase in hippocampal dentate spine density in the 6 hour post-training period of consolidation. Neuroscience 1998, 87:607-613.
59. O'Nuallain B., Freir D.B., Nicoll A.J., Risse E., Ferguson N., Herron C.E., Collinge J., Walsh D.M. Amyloid β-protein dimers rapidly form stable synaptotoxic protofibrils. J. Neurosci. 2010, 30:14411-14419.
60. O'Sullivan N.C., McGettigan P.A., Sheridan G.K., Pickering M., Conboy L., O'Connor J.J., Moynagh P.N., Higgins D.G., Regan C.M., Murphy K.J. Temporal change in gene expression in the rat dentate gyrus following passive avoidance learning. J. Neurochem. 2007, 101:1085-1098.
61. Parkin E.T., Watt N.T., Hussain I., Eckman E.A., Eckman C.B., Manson J.C., Baybutt H.N., Turner A.J., Hooper N.M. Cellular prion protein regulates β-secretase cleavage of the Alzheimer's amyloid precursor protein. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:11062-11067.
62. Paxinos G. The Rat Brain In Stereotaxic Coordinates 1986, Academic Press, Sydney.
63. Platano D., Fattoretti P., Balietti M., Giorgetti B., Casoli T., Di Stefano G., Bertoni-Freddari C., Aicardi G. Synaptic remodeling in hippocampal CA1 region of aged rats correlates with better memory performance in passive avoidance test. Rejuv. Res. 2008, 11:341-348.
64. Poling A., Morgan-Paisley K., Panos J.J., Kim E.M., O'Hare E., Cleary J.P., Lesne S., Ashe K.H., Porritt M., Baker L.E. Oligomers of the amyloid-beta protein disrupt working memory: confirmation with two behavioral procedures. Behav. Brain Res. 2008, 193:230-234.
65. Prince M.J. The 10/66 dementia research group - 10 years on. Indian J. Psychiatry 2009, 51:S8-S15.
66. Reddy P.H., Mani G., Park B.S., Jacques J., Murdoch G., Whetsell W., Kaye J., Manczak M. Differential loss of synaptic proteins in Alzheimer's disease: implications for synaptic dysfunction. J. Alzheimers Dis. 2005, 7:103-117. discussion 73-80.
67. Reed M.N., Hofmeister J.J., Jungbauer L., Welzel A.T., Yu C., Sherman M.A., Lesne S., LaDu M.J., Walsh D.M., Ashe K.H., Cleary J.P. Cognitive effects of cell-derived and synthetically derived Abeta oligomers. Neurobiol. Aging 2011, 32:1784-1794.
68. Richter J.D., Klann E. Making synaptic plasticity and memory last: mechanisms of translational regulation. Genes Dev. 2009, 23:1-11.
69. Rosenbaum R.S., Gao F., Richards B., Black S.E., Moscovitch M. "Where to?" remote memory for spatial relations and landmark identity in former taxi drivers with Alzheimer's disease and encephalitis. J. Cogn. Neurosci. 2005, 17:446-462.
70. Roullet P., Mileusnic R., Rose S.P., Sara S.J. Neural cell adhesion molecules play a role in rat memory formation in appetitive as well as aversive tasks. Neuroreport 1997, 8:1907-1911.
71. Sala Frigerio C., Fadeeva J.V., Minogue A.M., Citron M., Van Leuven F., Staufenbiel M., Paganetti P., Selkoe D.J., Walsh D.M. β-Secretase cleavage is not required for generation of the intracellular C-terminal domain of the amyloid precursor family of proteins. FEBS J. 2010, 277:1503-1518.
72. Sánchez C., Diǐaz-Nido J., Avila J. Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function. Prog. Neurobiol. 2000, 61:133-168.
73. Saura C.A., Valero J. The role of CREB signaling in Alzheimer's disease and other cognitive disorders. Rev. Neurosci. 2011, 22:153-169.
74. Scheff S.W., Price D.A. Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies. Neurobiol. Aging 2003, 24:1029-1046.
75. Scheff S.W., Price D.A., Schmitt F.A., DeKosky S.T., Mufson E.J. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 2007, 68:1501-1508.
76. Scheff S.W., Price D.A., Schmitt F.A., Mufson E.J. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol. Aging 2006, 27:1372-1384.
77. Selkoe D.J. Alzheimer's disease is a synaptic failure. Science 2002, 298:789-791.
78. Seymour C.M., Foley A.G., Murphy K.J., Regan C.M. Intraventricular infusions of anti-NCAM PSA impair the process of consolidation of both avoidance conditioning and spatial learning paradigms in Wistar rats. Neuroscience 2008, 157:813-820.
79. Shankar G.M., Leissring M.A., Adame A., Sun X., Spooner E., Masliah E., Selkoe D.J., Lemere C.A., Walsh D.M. Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Aβ assembly forms throughout life. Neurobiol. Dis. 2009, 36:293-302.
80. Shankar G.M., Li S., Mehta T.H., Garcia-Munoz A., Shepardson N.E., Smith I., Brett F.M., Farrell M.A., Rowan M.J., Lemere C.A., Regan C.M., Walsh D.M., Sabatini B.L., Selkoe D.J. Amyloid-[beta] protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 2008, 14:837-842.
81. Shankar G.M., Walsh D.M. Alzheimer's disease: synaptic dysfunction and Abeta. Mol. Neurodegener. 2009, 4:48.
82. Silva A.J., Kogan J.H., Frankland P.W., Kida S. CREB and memory. Ann. Rev. Neurosci. 1998, 21:127-148.
83. Small G.W. Early diagnosis of Alzheimer's disease: update on combining genetic and brain-imaging measures. Dialog. Clin. Neurosci. 2000, 2:241-246.
84. Small S.A., Perera G.M., DeLaPaz R., Mayeux R., Stern Y. Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease. Ann. Neurol. 1999, 45:466-472.
85. Sterio D.C. The unbiased estimation of number and sizes of arbitrary particles using the dissector. J. Microsc. 1984, 134:127-136.
86. Tabaton M., Nunzi M.G., Xue R., Usiak M., Autilio-Gambetti L., Gambetti P. Soluble amyloid beta-protein is a marker of Alzheimer amyloid in brain but not in cerebrospinal fluid. Biochem. Biophys. Res. Commun. 1994, 200:1598-1603.
87. Tang Y., Nyengaard J.R., De Groot D.M., Gundersen H.J. Total regional and global number of synapses in the human brain neocortex. Synapse 2001, 41:258-273.
88. Vlachos A., Korkotian E., Schonfeld E., Copanaki E., Deller T., Segal M. Synaptopodin regulates plasticity of dendritic spines in hippocampal neurons. J. Neurosci. 2009, 29:1017-1033.
89. Walsh D.M., Klyubin I., Fadeeva J.V., Cullen W.K., Anwyl R., Wolfe M.S., Rowan M.J., Selkoe D.J. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 2002, 416:535-539.
90. Walsh D.M., Minogue A.M., Sala Frigerio C., Fadeeva J.V., Wasco W., Selkoe D.J. The APP family of proteins: similarities and differences. Biochem. Soc. Trans. 2007, 35:416-420.
91. Yao P.J., Zhu M., Pyun E.I., Brooks A.I., Therianos S., Meyers V.E., Coleman P.D. Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease. Neurobiol. Dis. 2003, 12:97-109.
92. Zhao J., Fu Y., Yasvoina M., Shao P., Hitt B., O'Connor T., Logan S., Maus E., Citron M., Berry R., Binder L., Vassar R. β-Site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer's disease pathogenesis. J. Neurosci. 2007, 27:3639-3649.