Synaptic degeneration in Alzheimer's disease

Acta Neuropathologica

Volumn 118, Issue 1, 2009, Pages 167-179

  Arendt, Thomas ^a  

^a UNIVERSITY OF LEIPZIG   (Germany)

Author keywords

Alzheimer's disease; Cell cycle; Dementia; Morphoregulation; Neurodegeneration; Plasticity; Synapse

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; CHROMOGRANIN B; CLATHRIN ASSEMBLY PROTEIN; DREBRIN; NEUROGRANIN; NEUROMODULIN; RAB PROTEIN; SECRETOGRANIN II; SECRETONEURIN; SYNAPSIN I; SYNAPTOBREVIN; SYNAPTOPHYSIN; SYNAPTOSOMAL ASSOCIATED PROTEIN 25; SYNAPTOTAGMIN; SYNAPTOTAGMIN I; SYNTAXIN; TAU PROTEIN;

ALZHEIMER DISEASE; CELL CYCLE PROGRESSION; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CELL PROLIFERATION; COGNITIVE DEFECT; DOWN REGULATION; GENE OVEREXPRESSION; HUMAN; KNOCKOUT GENE; LOSS OF FUNCTION MUTATION; NERVE CELL; NERVE CELL NECROSIS; NERVE CELL PLASTICITY; NERVE DEGENERATION; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SYNAPTIC TRANSMISSION; WILD TYPE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BRAIN; CELL CYCLE; COGNITION DISORDERS; HUMANS; NERVE DEGENERATION; NEURONAL PLASTICITY; NEURONS; PHOSPHORYLATION; RECEPTORS, CELL SURFACE; SYNAPSES; TAU PROTEINS;

EID: 67349213205     PISSN: 00016322     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00401-009-0536-x     Document Type: Review

References (238)

1. Aoki C, Mahadomrongkul V, Fujisawa S, Habersat R, Shirao T (2007) Chemical and morphological alterations of spines within the hippocampus and entorhinal cortex precede the onset of Alzheimer's disease pathology in double knock-in mice. J Comp Neurol 505(4):352-362
2. Araki W, Kitaguchi N, Tokushima Y, Ishii K, Aratake H, Shimohama S, Nakamura S, Kimura J (1991) Trophic effect of beta-amyloid precursor protein on cerebral cortical neurons in culture. Biochem Biophys Res Commun 181:265-271
3. Aranchio O, Chao MV (2007) Neurotrophins, synaptic plasticity and dementia. Curr Opin Neurobiol 17:1-6
4. Arendt T (2001) Alzheimer's disease as a disorder of mechanisms underlaying structural brain self-organization. Commentary. Neuroscience 102:723-765
5. Arendt T (2003) Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways. The Dr. Jekyll and Mr. Hyde theory of Alzheimer's disease or The yin and yang of neuroplasticity. Progr Neurobiol 71:83-248
6. Arendt T (2008) Differentiation and de-differentiation - Neuronal cell cycle regulation during development and age-related neurodegenerative disorders. In: Lajtha A et al (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, pp 160-197
7. Arendt T, Bigl V, Tennstedt A, Arendt A (1985) Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer's disease. Neuroscience 14:1-14
8. Arendt T, Brükner MK (2007) Linking cell-cycle dysfunction in Alzheimer's disease to a failure of synaptic plasticity. Biochim Biophys Acta 1772(4):413-421
9. Arendt T, Gärtner U, Seeger G, Barmashenko G, Palm K, Mittmann T, Yan L, Hümmeke M, Behrbohm J, Brückner MK, Holzer M, Wahle P, Heumann R (2004) Neuronal activation of Ras regulates synaptic connectivity. Eur J Neurosci 19:2953-2966
10. Arendt T, Holzer M, Großmann A, Zedlick D, Brückner MK (1995) Increased expression and subcellular translocation of the mitogen-activated protein kinase kinase and mitogen-activated protein kinase in Alzheimer's disease. Neuroscience 68:5-18
11. Arendt T, Stieler J, Strijkstra AM, Hut RA, Rüdiger J, Van der Zee EA, Harkany T, Holzer M, Härtig W (2003) Reversible PHF-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals. J Neurosci 18:6972-6981
12. Arendt T, Rödel L, Gärtner U, Holzer M (1996) Expression of the cyclin-dependent kinase inhibitor p16 in Alzheimer's disease. Neuroreport 7:3047-3049
13. Bai F, Zhang Z, Watson DR, Yu H, Shi Y, Yuan Y, Zang Y, Zhu C, Qian Y (2008) Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment. Biol Psychiatry. 2008 Nov 22. [Epub ahead of print]
14. Bain A (1872) Mind and body. The theories of their relation. D. Appleton & Company, New York
15. Barnes CA (1994) Normal aging: Regionally specific changes in hippocampal synaptic transmission. Trends Neurosci 17:13-18
16. Bell KF, Bennett DA, Cuello AC (2007) Paradoxical upregulation of glutamatergic presynaptic boutons during mild cognitive impairment. J Neurosci 27:10810-10817
17. Bell KF, Zheng L, Fahrenholz F, Cuello AC (2008) ADAM-10 over-expression increases cortical synaptogenesis. Neurobiol Aging 29:554-565
18. Bertoni-Freddari C, Fattoretti P, Casoli T, Meier-Ruge W, Ulrich J (1990) Morphological adaptive response of the synaptic junctional zones in the human dentate gyrus during aging and Alzheimer's disease. Brain Res 517:69-75
19. Bertoni-Freddari C, Fattoretti P, Meier-Ruge W, Ulrich J (1989) Computer-assisted morphometry of synaptic plasticity during aging and dementia. Pathol Res Pract 185:799-802
20. Bertoni-Freddari C, Meier-Ruge W, Ulrich J (1988) Quantitative morphology of synaptic plasticity in the aging brain. Scanning Microsc 2:1027-1034
21. Binnington JC, Kalisch BE (2007) Nitric oxide synthase inhibitors modulate nerve growth factor-mediated regulation of amyloid precursor protein expression in PC12 cells. J Neurochem 101:422-433
22. Blennow K, Bogdanovic N, Alafuzoff I, Ekman R, Davidsson P (1996) Synaptic pathology in Alzheimer's disease: Relation to severity of dementia, but not to senile plaques, neurofibrillary tangles, or the ApoE4 allele. J Neural Transm 103(5):603-618
23. Boynton S, Tully T (1992) latheo, a new gene involved in associative learning and memory in Drosophila melanogaster, identified from P element mutagenesis. Genetics 131:655-672
24. Braak H, Braak E (1991) Neuropathological staging of Alzheimer related changes. Acta Neuropathol 82:239-259
25. Brown DF, Risser RC, Bigio EH, Tripp P, Stiegler A, Welch E, Eagan KP, Hladik CL, White CL 3rd (1998) Neocortical synapse density and Braak stage in the Lewy body variant of Alzheimer disease: A comparison with classic Alzheimer disease and normal aging. J Neuropathol Exp Neurol 57(10):955-960
26. Brun A, Liu X, Erikson C (1995) Synapse loss and gliosis in the molecular layer of the cerebral cortex in Alzheimer's disease and in frontal lobe degeneration. Neurodegeneration 4(2):171-177
27. Brunelli MP, Kowall NW, Lee JM, McKee AC (1991) Synaptophysin immunoreactivity is depleted in cortical laminae with dense dystrophic neurites and neurofibrillary tangles. J Neuropathol Exp Neurol 50:315
28. Buell SJ, Coleman PD (1979) Dendritic growth in the aged human brain and failure of growth in senile dementia. Science 206:854-856
29. Callahan LM, Vaules WA, Coleman PD (2002) Progressive reduction of synaptophysin message in single neurons in Alzheimer disease. J Neuropathol Exp Neurol 61(5):384-395
30. Callahan LM, Vaules WA, Coleman PD (1999) Quantitative decrease in synaptophysin message expression and increase in cathepsin D message expression in Alzheimer disease neurons containing neurofibrillary tangles. J Neuropathol Exp Neurol 58(3):275-287
31. Chang JW, Schumacher E, Coulter PM 2nd, Vinters HV, Watson JB (1997) Dendritic translocation of RC3/neurogranin mRNA in normal aging, Alzheimer disease and fronto-temporal dementia. J Neuropathol Exp Neurol 56:1105-1118
32. 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 (1999) Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 2:271-276
33. Clinton J, Blackman SE, Royston MC, Roberts GW (1994) Differential synaptic loss in the cortex in Alzheimer's disease: A study using archival material. Neuroreport 12; 5(4):497-500
34. Coleman PD, Yao PJ (2003) Synaptic slaughter in Alzheimer's disease. Neurobiol Aging 24:1023-1027
35. Cooke SF, Bliss TV (2006) Plasticity in the human central nervous system. Brain 129:1659-1673
36. Counts SE, Nadeem M, Lad SP, Wuu J, Mufson EJ (2006) Differential expression of synaptic proteins in the frontal and temporal cortex of elderly subjects with mild cognitive impairment. J Neuropathol Exp Neurol 65(6):592-601
37. Daigle I, Li C (1993) apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. PNAS 90:12045-12049
38. Davidsson P, Blennow K (1998) Neurochemical dissection of synaptic pathology in Alzheimer's disease. Int Psychogeriatr 10(1):11-23
39. Davidsson P, Jahn R, Bergquist J, Ekman R, Blennow K (1996) Synaptotagmin, a synaptic vesicle protein, is present in human cerebrospinal fluid: A new biochemical marker for synaptic pathology in Alzheimer disease? Mol Chem Neuropathol 27(2):195-210
40. Davies CA, Mann DM, Sumpter PQ, Yates PO (1987) 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 78:151-164
41. Dawson GR, Seabrook GR, Zheng H, Smith DW, Graham S, O'Dowd G, Bowery BJ, Boyce S, Trumbauer ME, Chen HY, Van der Ploeg LH, Sirinathsinghji DJ (1999) Age-related cognitive deficits, impaired long-term potention and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein. Neurosci 90:1-13
42. DeKosky ST, Harbaugh RE, Schmitt FA, Bakay RA, Chui HC, Knopman DS, Reeder TM, Shetter AG, Senter HJ, Markesbery WR (1992) Cortical biopsy in Alzheimer's disease: Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations. Intraventricular Bethanecol Study Group. Ann Neurol 32(5):625-632
43. DeKosky ST, Scheff SW, Styren SD (1996) Structural correlates of cognition in dementia: Quantification and assessment of synapse change. Neurodegeneration 5(4):417-421 Review
44. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity. Ann Neurol 27(5):457-464
45. Demoor J (1896) La plasticité morphologique des neurones cérébraux. Archives de Biologie 14:723-749
46. Dessi F, Colle MA, Hauw JJ, Duyckaerts C (1997) Accumulation of SNAP-25 immunoreactive material in axons of Alzheimer's disease. Neuroreport 8:3685-3689
47. Dickson DW, Crystal HA, Bevona C, Honer W, Vincent I, Davies P (1995) Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol Aging 16(3):285-298 discussion 298-304
48. Dinamarca MC, Colombres M, Cerpa W, Bonansco C, Inestrosa NC (2008) Beta-amyloid oligomers affect the structure and function of the postsynaptic region: Role of the Wnt signaling pathway. Neurodegener Dis 5:149-152
49. Duval M (1895) Hypothèses sur la physiologie des centres nerveux; théorie histologique du sommeil. Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 47:74-77
50. Duval M (1900) Les neurones. L'amiboïsme nerveux la théorie histologique du sommeil. Revue de l'École d'Anthropologie de Paris 10:37-71
51. Espinosa B, Zenteno R, Mena R, Robitaille Y, Zenteno E, Guevara J (2001) O-Glycosylation in sprouting neurons in Alzheimer disease, indicating reactive plasticity. J Neuropathol Exp Neurol 60:441-448
52. Featherstone DE, Broadie K (2000) Surprises from Drosophila: Genetic mechanisms of synaptic development and plasticity. Brain Res Bull 53(5):501-511
53. Fernandes MA, Proenca MT, Nogueira AJ, Oliveira LM, Santiago B, Santana I, Oliveira CR (1999) Effects of apolipoprotein E genotype on blood lipid composition and membrane platelet fluidity in Alzheimer's disease. Biochem Biophys Acta 1454:89-96
54. Fitzjohn SM, Morton RA, Kuenzi F, Rosahl TW, Shearman M, Lewis H, Smith D, Reynolds DS, Davies CH, Collingridge GL, Seabrook GR (2001) Age-related impairment of synaptic transmission but normal long-term potentiation in transgenic mice that overexpress the human APP695SWE mutant form of amyloid precursor protein. J Neurosci 21:4691-4698
55. Flood DG, Coleman PD (1986) Failed compensatory dendritic growth as a pathophysiological process in Alzheimer's disease. Can J Neurol Sci 13(Suppl. 4):475-479
56. Fukumoto H, Cheung BS, Hyman BT, Irizarry MC (2002) Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol 59(9):1381-1389
57. Furukawa K, Sopher BL, Rydel RE, Begley JG, Pham DG, Martin GM, Fox M, Mattson MP (1996) Increased activity-regulating and neuroprotective efficacy of alpha-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain. J Neurochem 67:1882-1896
58. Gabriel A, Klussmann FW, Igelmund P (1998) Rapid temperature changes induce adenosine-mediated depression of synaptic transmission in hippocampal slices from rats (non-hibernators). Neuroscience 86:67-77
59. Gabriel SM, Haroutunian V, Powchik P, Honer WG, Davidson M, Davies P, Davis KL (1997) Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia. Arch Gen Psychiatry 54(6):559-66. Erratum in: Arch Gen Psychiatry 1997 54(10):912
60. Gärtner U, Holzer M, Arendt T (1999) Elevated expression of p21 ras is an early event in Alzheimer's disease and precedes neurofibrillary degeneration. Neuroscience 91:1-5
61. Gärtner U, Holzer M, Heumann R, Arendt T (1995) Induction of p21 ras in Alzheimer pathology. Neuroreport 6:1441-1444
62. Giacchino J, Criado JR, Games D, Henriksen S (2000) In vivo synaptic transmission in young and aged amyloid precursor protein transgenic mice. Brain Res 876:185-190
63. Gibson PH (1983) EM study of the numbers of cortical synapses in the brains of ageing people and people with Alzheimer-type dementia. Acta Neuropathol (Berl) 62:127-133
64. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roques P, Tabot C, Williamson R, Rossor M, Hardy J (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349:704-706
65. Götz J, Ittner LM, Kins S (2006) Do axonal defects in tau and amyloid precursor protein transgenic animals model axonopathy in Alzheimer's disease? J Neurochem 98:993-1006
66. Gonatas NK, Anderson W, Evangelista I (1967) The contribution of altered synapses in the senile plaque: An electron microscopic study in Alzheimer's dementia. J Neuropathol. Exp Neurol 26:25-39
67. Gottfries CG, Karlsson I, Svennerholm L (1996) Membrane components separate early-onset Alzheimer's disease from senile dementia of the Alzheimer type. Int Psychogeriatr 8:365-372
68. Gralle M, Ferreira ST (2007) Structure and functions of the human amyloid precursor protein: The whole is more than the sum of its parts. Progr Neurobiol 82:11-32
69. Gunawardena S, Goldstein LS (2001) Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila. Neuron 32:389-401
70. Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, Lieberburg I, Koo EH, Schenk D, Teplow DB, Selkoe DJ (1992) Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 359:322-325
71. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101-112
72. Hamos JE, DeGennaro LJ, Drachman DA (1989) Synaptic loss in Alzheimer's disease and other dementias. Neurol 39:355-361
73. Hansen LA, Daniel SE, Wilcock GK, Love S (1998) Frontal cortical synaptophysin in Lewy body diseases: Relation to Alzheimer's disease and dementia. J Neurol Neurosurg Psychiatry 64:653-656
74. Härtig W, Stieler J, Boerema AS, Wolf J, Schmidt U, Weißfuß J, Bullmann T, Strijkstra AM, Arendt T (2007) Hamster model of tau hyperphosphorylation: Selective vulnerability of cholinergic forebrain neurons during hibernation - implications for Alzheimer's disease. Eur J Neurosci 25:69-80
75. Harigaya Y, Shoji M, Shirao T, Hirai S (1996) Disappearance of actin-binding protein, drebrin, from hippocampal synapses in Alzheimer's disease. J Neurosci Res 43:87-92
76. Hasselmo ME (1997) A computational model of the progression of Alzheimer's disease. MD Comput 14:181-191
77. Hatanpää K, Isaacs KR, Shirao T, Brady DR, Rapoport SI (1999) Loss of proteins regulating synaptic plasticity in normal aging of the human brain and in Alzheimer disease. J Neuropathol Exp Neurol 58:637-643
78. Heber S, Herms J, Gajic V, Hainfellner J, Aguzzi A, Rülicke T, von Kretzschmar H, von Koch C, Sisodia S, Tremml P, Lipp HP, Wolfer DP, Müller U (2000) Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J Neurosci 20:7951-7963
79. Heffernan JM, Eastwood SL, Nagy Z, Sanders MW, McDonald B, Harrison PJ (1998) Temporal cortex synaptophysin mRNA is reduced in Alzheimer's disease and is negatively correlated with the severity of dementia. Exp Neurol 150(2):235-239
80. Heinonen O, Lehtovirta M, Soininen H, Helisalmi S, Mannermaa A, Sorvari H, Kosunen O, Paljärvi L, Ryynänen M, Riekkinen PJ Sr (1995) Alzheimer pathology of patients carrying apolipoprotein E epsilon 4 allele. Neurobiol Aging 16(4):505-513
81. Heinonen O, Soininen H, Sorvari H, Kosunen O, Paljärvi L, Koivisto E, Riekkinen PJ Sr (1995) Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in Alzheimer's disease. Neuroscience 64(2):375-384
82. Herms J, Anliker B, Heber S, Ring S, Fuhrmann M, Kretzschmar H, Sisodia S, Müller U (2004) Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members. EMBO J 23:4106-4115
83. Honer WG, Dickson DW, Gleeson J, Davies P (1992) Regional synaptic pathology in Alzheimer's disease. Neurobiol Aging 13(3):375-382
84. Honer WG (2003) Pathology of presynaptic proteins in Alzheimer's disease: More than simple loss of terminals. Neurobiol Aging 24:1047-1062
85. Horn D, Levy N, Ruppin E (1996) Neuronal-based synaptic compensation: A computational study in Alzheimer's disease. Neural Comput 8:1227-1243
86. Horwitz B, Grady CL, Schlageter NL, Duara R, Rapoport SI (1987) Intercorrelations of regional cerebral glucose metabolic rates in Alzheimer's disease. Brain Res 407:294-306
87. Hu NW, Smith IM, Walsh DM, Rowan MJ (2008) Soluble amyloid-beta peptides potently disrupt hippocampal synaptic plasticity in the absence of cerebrovascular dysfunction in vivo. Brain 131:2414-2424
88. Huang Z, Zang K, Reichardt LF (2005) The origin recognition core complex regulates dendrite and spine development in postmitotic neurons. J Cell Biol 170:527-535
89. Huber G, Bailly Y, Martin JR, Mariani J, Brugg B (1997) Synaptic beta-amyloid precursor proteins increase with learning capacity in rats. Neurosci 80:313-320
90. Hut RA, de Wilde MC, Strijkstra AM, Van der Zee EA, Daan S (2001) Neuronal changes in the hippocampus and SCN of hibernating ground squirrels. Soc Neurosci Abstr 27:535.11
91. Ishida A, Furukawa K, Keller JN, Mattson MP (1997) Secreted form of beta-amyloid precursor protein shifts the frequency dependency for induction of LTD, and enhances LTP in hippocampal slices. Neuroreport 8:2133-2137
92. Johnson SC, Schmitz TW, Moritz CH, Meyerand ME, Rowley HA, Alexander AL, Hansen KW, Gleason CE, Carlsson CM, Ries ML, Asthana S, Chen K, Reiman EM, Alexander GE (2006) Activation of brain regions vulnerable to Alzheimer's disease: The effect of mild cognitive impairment. Neurobiol Aging 27:1604-1612
93. Jorgensen OS, Balázs R (1993) Plastic neuronal changes in Alzheimer's disease associated with activation of astrocytes and enhanced neurotrophic activity. In: Corain B, Iqbal K, Nicolini M, Winblad B, Wisniewski H, Zatta P (eds) Alzheimer's disease: Advances in clinical and basic research. Wiley, Chichester, pp 189-198
94. Katzman R (1986) Alzheimer's disease. N Engl J Med 314:964-973
95. Kaufmann WA, Barnas U, Humpel C, Nowakowski K, DeCol C, Gurka P, Ransmayr G, Hinterhuber H, Winkler H, Marksteiner J (1998) Synaptic loss reflected by secretoneurin-like immunoreactivity in the human hippocampus in Alzheimer's disease. Eur J Neurosci 10(3):1084-1094
96. Kavanau JL (1997) Memory, sleep and the evolution of mechanisms of synaptic efficacy maintenance. Neuroscience 79:7-44
97. Kirazov E, Kirazov L, Bigl V, Schliebs R (2001) Ontogenetic changes in protein level of amyloid precursor protein (APP) in growth cones and synaptosomes from rat brain and prenatal expression pattern of APP mRNA isoforms in developing rat embryo. Int J Dev Neurosci 19:287-296
98. Klyubin I, Walsh DM, Cullen WK, Fadeeva JV, Anwyl R, Selkoe DJ, Rowan MJ (2004) Soluble Arctic amyloid beta protein inhibits hippocampal long-term potentiation in vivo. Eur J Neurosci 19:2839-2846
99. Klyubin I, Walsh DM, Lemere CA, Cullen WK, Shankar GM, Betts V, Spooner ET, Jiang L, Anwyl R, Selkoe DJ, Rowan MJ (2005) Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nat Med 11:556-561
100. 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 (2009) Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci USA 106(10):4012-4017
101. Koo EH, Sisodia SS, Archer DR, Martin LJ, Weidemann A, Beyreuther K, Fischer P, Masters CL, Price DL (1990) Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. PNAS 87:1561-1565
102. Korade Z, Kenworthy AK (2008) Lipid rafts, cholesterol, and the brain. Neuropharmacology 55(8):1265-1273
103. Krilowicz BL, Glotzbach SF, Heller HC (1988) Neuronal activity during sleep and complete bouts of hibernation. Am J Physiol 255:R1008-R1019
104. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL (1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA 95:6448-6453
105. Lassmann H, Fischer P, Jellinger K (1993) Synaptic pathology of Alzheimer's disease. Ann N Y Acad Sci 695:59-64
106. Lassmann H, Weiler R, Fischer P, Bancher C, Jellinger K, Floor E, Danielczyk W, Seitelberger F, Winkler H (1992) Synaptic pathology in Alzheimer's disease: Immunological data for markers of synaptic and large dense-core vesicles. Neuroscience 46:1-8
107. Lechner T, Adlassnig C, Humpel C, Kaufmann WA, Maier H, Reinstadler-Kramer K, Hinterhölzl J, Mahata SK, Jellinger KA, Marksteiner J (2004) Chromogranin peptides in Alzheimer's disease. Exp Gerontol 39(1):101-113
108. Lépine MR (1895) Théorie mécanique de la paralysie hystérique, du somnambulisme, du sommeil naturel et de la distraction. Soc Biol 5:85-86
109. Leuba G, Savioz A, Vernay A, Carnal B, Kraftsik R, Tardif E, Riederer I, Riederer BM (2008) Differential changes in synaptic proteins in the Alzheimer frontal cortex with marked increase in PSD-95 postsynaptic protein. J Alzheimers Dis 15:139-151
110. Lewis DA, Campbell MJ, Terry RD, Morrison JH (1987) Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: A quantitative study of visual and auditory cortices. J Neurosci 7:1799-1808
111. Leyssen M, Ayaz D, Hébert SS, Reeve S, De Strooper B, Hassan BA (2005) Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain. EMBO J 24:2944-2955
112. Lippa CF, Hamos JE, Pulaski-Salo D, DeGennaro LJ, Drachman DA (1992) Alzheimer's disease and aging: Effects on perforant pathway perikarya and synapses. Neurobiol Aging 13:405-411
113. Liu X, Erikson C, Brun A (1996) Cortical synaptic changes and gliosis in normal aging, Alzheimer's disease and frontal lobe degeneration. Dementia 7(3):128-134
114. Löffler J, Huber G (1992) β-amyloid precirsor protein isoforms in various rat brain regions and during development. J. Neurochem 59:1316-1324
115. López-Sánchez N, Müller U, Frade JM (2005) Lengthening of G2/mitosis in cortical precursors from mice lacking β-amyloid precursor protein. Neurosci 130:51-60
116. Lubec G, Nonaka M, Krapfenbauer K, Gratzer M, Cairns N, Fountoulakis M (1999) Expression of the dihydropyrimidinase related protein 2 (DRP-2) in Down syndrome and Alzheimer's disease brain is downregulated at the mRNA and dysregulated at the protein level. J Neural Transm, Suppl. 57:161-177
117. Lue LF, Brachova L, Civin WH, Rogers J (1996) Inflammation, A beta deposition, and neurofibrillary tangle formation as correlates of Alzheimer's disease neurodegeneration. J Neuropathol Exp Neurol 55(10):1083-1088
118. Lugaro E (1895) Sulle Modificazioni delle cellule nervose. Lo Sperimentale 49:159-193
119. Lugaro E (1898) Sulle modificazioni morfologiche funzionali die dendriti delle cellule nervose. Rivista di Patologia Nervosa e Mentale 3:337-359
120. Lugaro E (1899) I recenti progressi dell'anatomia del sistema nervoso in rapporto alla psicologia ed alla psichiatria. Rivista di Patologia Nervosa e Mentale 4:481-514
121. Lugaro E (1900) I recenti progressi dell'anatomia del sistema nervoso in rapporto alla psicologia ed alla psichiatria. Rivista Sperimentale di Freniatria e Medicina Legale delle Alienazioni Mentali 26:831-894
122. Luo LQ, Martin-Morris LE, White K (1990) Identification, secretion, and neural expression of APPL, a Drosophila protein similar to human amyloid protein precursor. J Neurosci 10:3849-3861
123. Ma H, Lesné S, Kotilinek L, Steidl-Nichols JV, Sherman M, Younkin L, Younkin S, Forster C, Sergeant N, Delacourte A, Vassar R, Citron M, Kofuji P, Boland LM, Ashe KH (2007) Involvement of beta-site APP cleaving enzyme 1 (BACE1) in amyloid precursor protein-mediated enhancement of memory and activity-dependent synaptic plasticity. PNAS 104:8167-8172
124. Magara F, Müller U, Li ZW, Lipp HP, Weissmann C, Stagljar M, Wolfer DP (1999) Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein. PNAS 96:4656-4661
125. Magariños AM, McEwen BS, Saboureau M, Pevet P (2006) Rapid and reversible changes in intrahippocampal connectivity during the course of hibernation in European hamsters. Proc Natl Acad Sci USA 103:18775-18780
126. Majocha RE, Jungalwala FB, Rodenrys A, Marotta CA (1989) Monoclonal antibody to embryonic CNS antigen A2B5 provides evidence for the involvement of membrane components at sites of Alzheimer degeneration and detects sulfatides as well as gangliosides. J Neurochem 53:953-961
127. Marksteiner J, Kaufmann WA, Gurka P, Humpel C (2002) Synaptic proteins in Alzheimer's disease. J Mol Neurosci 18(1-2):53-63
128. Marksteiner J, Lechner T, Kaufmann WA, Gurka P, Humpel C, Nowakowski C, Maier H, Jellinger KA (2000) Distribution of chromogranin B-like immunoreactivity in the human hippocampus and its changes in Alzheimer's disease. Acta Neuropathol 100(2):205-212
129. Martin-Morris LE, White K (1990) The Drosophila transcript encoded by the beta-amyloid protein precursor-like gene is restricted to the nervous system. Development 110:185-195
130. Masliah E (1995) Mechanisms of synaptic dysfunction in Alzheimer's disease. Histol Histopathol 10:509-519
131. Masliah E, Alford M, DeTeresa R, Mallory M, Hansen L (1996) Deficient glutamate transport is associated with neurodegeneration in Alzheimer's disease. Ann Neurol 40(5):759-766
132. Masliah E, Ellisman M, Carragher B, Mallory M, Young S, Hansen L, DeTeresa R, Terry RD (1992) Three-dimensional analysis of the relationship between synaptic pathology and neuropil threads in Alzheimer disease. J Neuropathol Exp Neurol 51(4):404-414
133. Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DW Jr, Morris JC (2001) Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurol 56:127-129
134. Masliah E, Mallory M, Ge N, Alford M, Veinbergs I, Roses AD (1995) Neurodegeneration in the central nervous system of apoE-deficient mice. Exp Neurol 136(2):107-122
135. Masliah E, Mallory M, Hansen L, DeTeresa R, Alford M, Terry R (1994) Synaptic and neuritic alterations during the progression of Alzheimer's disease. Neurosci Lett 174(1):67-72
136. Masliah E, Mallory M, Hansen L, DeTeresa R, Terry RD (1993) Quantitative synaptic alterations in the human neocortex during normal aging. Neurology 43:192-197
137. Masliah E, Terry R (1993) The role of synaptic proteins in the pathogenesis of disorders of the central nervous system. Brain Pathol 3(1):77-85
138. Masliah E, Terry R (1994) The role of synaptic pathology in the mechanisms of dementia in Alzheimer's disease. Clin Neurosci 1:192-198
139. Masliah E, Terry RD, Alford M, DeTeresa R, Hansen LA (1991) Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease. Am J Pathol 138(1):235-246
140. Masliah E, Terry RD, DeTeresa RM, Hansen LA (1989) Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer disease. Neurosci Lett 103(2):234-239
141. Masliah E, Terry RD, Mallory M, Alford M, Hansen LA (1990) Diffuse plaques do not accentuate synapse loss in Alzheimer's disease. Am J Pathol 137(6):1293-1297
142. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. PNAS 82:4245-4249
143. Mattson MP, Cheng B, Culwell AR, Esch FS, Lieberburg I, Rydel RE (1993) Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein. Neuron 10:243-254
144. Mattson MP (1994) Secreted forms of beta-amyloid precursor protein modulate dendrite outgrowth and calcium responses to glutamate in cultured embryonic hippocampal neurons. J Neurobiol 25:439-450
145. Meziane H, Dodart JC, Mathis C, Little S, Clemens J, Paul SM, Ungerer A (1998) Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in normal and amnestic mice. Proc Natl Acad Sci USA 95:12683-12688
146. Mikkonen M, Soininen H, Tapiola T, Alafuzoff I, Miettinen R (1999) Hippocampal plasticity in Alzheimer's disease: Changes in highly polysialylated NCAM immunoreactivity in the hippocampal formation. Eur J Neurosci 11:1754-1764
147. Millesi E, Prossinger H, Dittami JP, Fieder M (2001) Hibernation effects on memory in European ground squirrels (Spermophilus citellus). J Biol Rhythm 16:264-271
148. Milward EA, Papadopoulos R, Fuller SJ, Moir RD, Small D, Beyreuther K, Masters CL (1992) The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth. Neuron 9:129-137
149. Minger SL, Honer WG, Esiri MM, McDonald B, Keene J, Nicoll JA, Carter J, Hope T, Francis PT (2001) Synaptic pathology in prefrontal cortex is present only with severe dementia in Alzheimer disease. J Neuropathol Exp Neurol 60(10):929-936
150. Morrison JH, Hof PR, Campell MJ, DeLima AD, Voigt T, Bouras C, Cox K, Young WG (1990) Cellular pathology in Alzheimer's disease: Implications for corticocortical disconnection and differential vulnerability. In: Rapoport SI, Petit H, Leys D, Christen Y (eds) Imaging, Cerebral Topography and Alzheimer's disease. Research and Perspectives in Alzheimer's disease. Springer, Berlin, pp 19-40
151. Mucke L, Masliah E, Johnson WB, Ruppe MD, Alford M, Rockenstein EM, Forss-Petter S, Pietropaolo M, Mallory M, Abraham CR (1994) Synaptotrophic effects of human amyloid beta protein precursors in the cortex of transgenic mice. Brain Res 666:151-167
152. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L (2000) High-level neuronal expression of Aβ1-42 in wild-type human amyloid protein precursor transgenic mice: Synaptotoxicity without plaque formation. J Neurosci 20:4050-4058
153. Mukaetova-Ladinska EB, Garcia-Siera F, Hurt J, Gertz HJ, Xuereb JH, Hills R, Brayne C, Huppert FA, Paykel ES, McGee M, Jakes R, Honer WG, Harrington CR, Wischik CM (2000) Staging of cytoskeletal and beta-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer's disease. Am J Pathol 157(2):623-636
154. Muntané G, Dalfó E, Martinez A, Ferrer I (2008) Phosphorylation of tau and alpha-synuclein in synaptic-enriched fractions of the frontal cortex in Alzheimer's disease, and in Parkinson's disease and related alpha-synucleinopathies. Neuroscience 152:913-923
155. Nagy Z, Esiri MM, Smith AD (1997) Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropathol 93:294-300
156. Origlia N, Righi M, Capsoni S, Cattaneo A, Fang F, Stern DM, Chen JX, Schmidt AM, Arancio O, Yan SD, Domenici L (2008) Receptor for advanced glycation end product-dependent activation of p38 mitogen-activated protein kinase contributes to amyloid-beta-mediated cortical synaptic
157. Perdahl E, Adolfsson R, Alafuzoff I, Albert KA, Nestler EJ, Greengard P, Winblad B (1984) Synapsin I (protein I) in different brain regions in senile dementia of Alzheimer type and in multi-infarct dementia. J Neural Transm 60(2):133-141
158. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 25;2(6150):1457-1459
159. Phinney AL, Calhoun ME, Wolfer DP, Lipp HP, Zheng H, Jucker M (1999) No hippocampal neuron or synaptic bouton loss in learning-impaired aged beta-amyloid precursor protein-null mice. Neurosci 90:1207-1216
160. Pinto S, Quintana DG, Smith P, Mihalek RM, Hou ZH, Boynton S, Jones CJ, Hendricks M, Velinzon K, Wohlschlegel JA, Austin RJ, Lane WS, Tully T, Dutta A (1999) latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant. Neuron 23:45-54
161. Plant LD, Boyle JP, Smith IF, Peers C, Pearson HA (2003) The production of amyloid beta peptide is a critical requirement for the viability of central neurons. J Neurosci 23:5531-5535
162. Popov VI, Bocharova LS (1992) Hibernation-induced structural changes in synaptic contracts between mossy fibres and hippocampal neurons. Neuroscience 48:53-62
163. Popov VL, Bocharova LS, Bragin AG (1992) Repeated changes of dendritic morphology in the hippocampus of ground squirrels in the course of hibernation. Neuroscience 48:45-51
164. Puzzo D, Privitera L, Leznik E, Fä M, Staniszewski A, Palmeri A, Arancio O (2008) Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci 28:14537-14545
165. Rabl-Rückhard (1890) Sind die Ganglienzellen amöboid? Eine Hypothese zur Mechanik psychischer Vorgänge. Neurologisches Centralblatt 9:199-200
166. Ramón y Cajal S (1894) The Croonian lecture. La fine structure des centres nerveux. Proceedings of the Royal Society of London. vol. LV. Harrison and Sons, London, pp 444-468
167. Ramón y Cajal S (1911) Histologie du systeme nerveux. A. Maloine. Paris. (This is the second edition, in French, of the Textura del sistema nervioso del hombre y los vertebrados of 1899. Quotations here are from the English translation by N. and L. Swanson, vol 1. Oxford University Press 1995, New York
168. Ramón y Cajal S (1928) Degeneration and regeneration of the nervous system. Oxford University Press, London
169. Rapoport SI (1999) In vivo PET imaging and postmortem studies suggest potentially reversible and irreversible stages of brain metabolic failure in Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci 249(Suppl 3):46-55
170. Reddy PH, Mani G, Park BS, Jacques J, Murdoch G, Whetsell W Jr, Kaye J, Manczak M (2005) Differential loss of synaptic proteins in Alzheimer's disease: Implications for synaptic dysfunction. J Alzheimers Dis 7:103-117
171. Roch JM, Masliah E, Roch-Levecq AC, Sundsmo MP, Otero DA, Veinbergs I, Saitoh T (1994) Increase of synaptic density and memory retention by a peptide representing the trophic domain of the amyloid beta/A4 protein precursor. PNAS 91:7450-7454
172. Rohrbough J, Pinto S, Mihalek RM, Tully T, Broadie K (1999) latheo, a Drosophila gene involved in learning, regulates functional synaptic plasticity. Neuron 23:55-70
173. Rosen DR, Martin-Morris L, Luo LQ, White K (1989) A Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor. PNAS 86:2478-2482
174. Rossner S, Ueberham U, Schliebs R, Perez-Polo JR, Bigl V (1998) p75 and TrkA receptor signaling independently regulate amyloid precursor protein mRNA expression, isoform composition, and protein secretion in PC12 cells. J. Neurochem 71:757-766
175. Rossner S, Ueberham U, Schliebs R, Perez-Polo JR, Bigl V (1998) The regulation of amyloid precursor protein metabolism by cholinergic mechanisms and neurotrophin receptor signaling. Progr Neurobiol 56:541-569
176. Rowan MJ, Klyubin I, Wang Q, Hu NW, Anwyl R (2007) Synaptic memory mechanisms: Alzheimer's disease amyloid beta-peptide-induced dysfunction. Biochem Soc Trans 35:1219-1223
177. Ruiz-León Y, Pascual A (2004) Regulation of beta-amyloid precursor protein expression by brain-derived neurotrophic factor involves activation of both the Ras and phosphatidylinositide 3-kinase signalling pathways. J Neurochem 88:1010-1018
178. Sabo SL, Ikin AF, Buxbaum JD, Greengard P (2003) The amyloid precursor protein and its regulatory protein, FE65, in growth cones and synapses in vitro and in vivo. J Neurosci 23:5407-5415
179. Salbaum JM, Ruddle FH (1994) Embryonic expression pattern of amyloid protein precursor suggests a role in differentiation of specific subsets of neurons. J Exp Zool 269:116-127
180. Samuel W, Alford M, Hofstetter CR, Hansen L (1997) Dementia with Lewy bodies versus pure Alzheimer disease: Differences in cognition, neuropathology, cholinergic dysfunction, and synapse density. J Neuropathol Exp Neurol 56(5):499-508
181. Samuel W, Terry RD, DeTeresa R, Butters N, Masliah E (1994) Clinical correlates of cortical and nucleus basalis pathology in Alzheimer dementia. Arch Neurol 51(8):772-778
182. Scheff SW, DeKosky ST, Price DA (1990) Quantitative assessment of cortical synaptic density in Alzheimer's disease. Neurobiol Aging 11(1):29-37
183. Scheff SW, Price DA, Schmitt FA, DeKosky ST, Mufson EJ (2007) Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 68:1501-1508
184. Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging 27(10):1372-1384
185. Schmetsdorf S, Gärtner U, Arendt T (2005) Expression of cell cycle-related proteins in developing and adult mouse hippocampus. Int J Dev Neurosci 23:101-112
186. Schmetsdorf S, Gärtner U, Arendt T (2007) Constitutive expression of functionally active cyclin-dependent kinases and their binding partners suggests noncanonical functions of cell cycle regulators in differentiated neurons. Cereb. Cortex 17(8):1821-1829
187. Schubert W, Prior R, Weidemann A, Dircksen H, Multhaup G, Masters CL, Beyreuther K (1991) Localization of Alzheimer beta A4 amyloid precursor protein at central and peripheral synaptic sites. Brain Res 563:184-194
188. Seabrook GR, Smith DW, Bowery BJ, Easter A, Reynolds T, Fitzjohn SM, Morton RA, Zheng H, Dawson GR, Sirinathsinghji DJ, Davies CH, Collingridge GL, Hill RG (1999) Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. Neuropharmacology 38:349-359
189. Seeger G, Gärtner U, Ueberham U, Rohn S, Arendt T (2009) FAD-mutation of APP is associated with a loss of its synaptotrophic activity. Neurobiology of Disease (under revision)
190. Selkoe DJ (2008) Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav Brain Res 192:106-113
191. Selkoe DJ (1994) Normal and abnormal biology of the beta-amyloid precursor protein. Annu Rev Neurosci 17:489-517
192. 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 (2008) Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 14:837-842
193. Shigematsu K, McGeer PL, McGeer EG (1992) Localization of amyloid precursor protein in selective postsynaptic densities of rat cortical neurons. Brain Res 592:353-357
194. Shimohama S, Fujimoto S, Sumida Y, Akagawa K, Shirao T, Matsuoka Y, Taniguchi T (1998) Differential expression of rat brain synaptic proteins in development and aging. Biochem Biophys Res Commun 251(1):394-398
195. Shimohama S, Kamiya S, Taniguchi T, Akagawa K, Kimura J (1997) Differential involvement of synaptic vesicle and presynaptic plasma membrane proteins in Alzheimer's disease. Biochem Biophys Res Commun 236(2):239-242
196. Simpson IA, Chundu KR, Davies-Hill T, Honer WG, Davies P (1994) Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease. Ann Neurol 35(5):546-551
197. Slunt HH, Thinakaran G, Von Koch C, Lo AC, Tanzi RE, Sisodia SS (1994) Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP). J Biol Chem 269:2637-2644
198. Smith-Swintosky VL, Pettigrew LC, Craddock SD, Culwell AR, Rydel RE, Mattson MP (1994) Secreted forms of beta-amyloid precursor protein protect against ischemic brain injury. J Neurochem 63:781-784
199. Sorg C, Riedl V, Mühlau M, Calhoun VD, Eichele T, Läer L, Drzezga A, Förstl H, Kurz A, Zimmer C, Wohlschläger AM (2007) Selective changes of resting-state networks in individuals at risk for Alzheimer's disease. Proc Natl Acad Sci USA 104:18760-18765
200. Sperling R (2007) Functional MRI studies of associative encoding in normal aging, mild cognitive impairment, and Alzheimer's disease. Ann N Y Acad Sci 1097:146-155
201. Stieler JT, Boerema AS, Bullmann T, Kohl F, Strijkstra AM, Barnes BM, Arendt T (2008) Activity-state profile of tau kinases in hibernating animals. In: Lovegrove BG, McKechnie AE (eds) Hypometabolism in animals: hibernation, torpor and cryobiology. University of KwaZulu-Nata, Pietermaritzburg, pp 133-142
202. Stieler JT, Bullmann T, Kohl F, Barnes BM, Arendt T (2009) PHF-like tau phosphorylation in mammalian hibernation is not associated with p25-formation. J Neural Transm 116(3):345-350
203. Strijkstra AM, Hut RA, de Wilde MC, Stieler J, Van der Zee EA (2003) Hippocampal synaptophysin immunoreactivity is reduced during natural hypothermia in ground squirrels. Neurosci Lett 344:29-32
204. Supekar K, Menon V, Rubin D, Musen M, Greicius MD (2008) Network analysis of intrinsic functional brain connectivity in Alzheimer's disease. PLoS Comput Biol 4(6):e1000100
205. Svennerholm L, Gottfries CG (1994) Membrane lipids, selectively diminished in Alzheimer brains, suggest synapse loss as a primary event in early-onset form (type I) and demyelination in late-onset form (type II). J Neurochem 62:1039-1047
206. Sze CI, Bi H, Kleinschmidt-DeMasters BK, Filley CM, Martin LJ (2000) Selective regional loss of exocytotic presynaptic vesicle proteins in Alzheimer's disease brains. J Neurol Sci 175(2):81-90
207. Sze CI, Troncoso JC, Kawas C, Mouton P, Price DL, Martin LJ (1997) Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease. J Neuropathol Exp Neurol 56(8):933-944
208. Takahashi RH, Capetillo-Zarate E, Lin MT, Milner TA, Gouras GK (2008) Co-occurrence of Alzheimer's disease beta-amyloid and tau pathologies at synapses. Neurobiol Aging 2008 Sep 2. [Epub ahead of print]
209. Tanzi RE, Gusella JF, Watkins PC, Bruns GA, St George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL (1987) Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235:880-884
210. Tanzi E (1893) I fatti e le induzioni nell'odierna istologia del sistema nervoso. Rivista Sperimentale di Frenetria e Medicina Legale della Alienzioni mentali 19:419-472
211. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann Neurol 30(4):572-580
212. Terry RD (1996) The pathogenesis of Alzheimer disease: An alternative to the amyloid hypothesis. J Neuropathol Exp Neurol 55(10):1023-1025
213. Thornton E, Vink R, Blumbergs PC, Van Den Heuvel C (2006) Soluble amyloid precursor protein alpha reduces neuronal injury and improves functional outcome following diffuse traumatic brain injury in rats. Brain Res 1094:38-46
214. Torroja L, Packard M, Gorczyca M, White K, Budnik V (1999) The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction. J Neurosci 19:7793-7803
215. van Gehuchten A (1900) Anatomie du systéme nerveux de l'homme. 3rd edn. Louvain
216. Villa A, Latasa MJ, Pascual A (2001) Nerve growth factor modulates the expression and secretion of beta-amyloid precursor protein through different mechanisms in PC12 cells. J Neurochem 77:1077-1084
217. Vincent I, Rosado M, Davies P (1996) Mitotic mechanisms in Alzheimer's disease? J Cell Biol 132:413-425
218. von der Ohe CG, Garner CC, Darian-Smith C, Heller HC (2007) Synaptic protein dynamics in hibernation. J Neurosci 27:84-92
219. von Koch CS, Zheng H, Chen H, Trumbauer M, Thinakaran G, van der Ploeg LH, Price DL, Sisodia SS (1997) Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol Aging 18:661-669
220. von Kölliker (1895) Kritik der Hypothesen von Rabl-Rückhard und Duval über amoeboide Bewegungen der Neurodendren. Sitzungsberichte der physik.-med. Gesellschaft: 38-42
221. Wakabayashi K, Honer WG, Masliah E (1994) Synapse alterations in the hippocampal-entorhinal formation in Alzheimer's disease with and without Lewy body disease. Brain Res 667(1):24-32
222. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535-539
223. Walsh DM, Selkoe DJ (2004) Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron 44:181-193
224. Wang L, Zang Y, He Y, Liang M, Zhang X, Tian L, Wu T, Jiang T, Li K (2006) Changes in hippocampal connectivity in the early stages of Alzheimer's disease: Evidence from resting state fMRI. Neuroimage 31:496-504
225. Wang P, Yang G, Mosier DR, Chang P, Zaidi T, Gong YD, Zhao NM, Dominguez B, Lee KF, Gan WB, Zheng H (2005) Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-like protein 2. J Neurosci 25:1219-1225
226. Wasco W, Bupp K, Magendantz M, Gusella JF, Tanzi RE, Solomon F (1992) Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor. PNAS 89:10758-10762
227. Wasco W, Gurubhagavatula S, Paradis MD, Romano DM, Sisodia SS, Hyman BT, Neve RL, Tanzi RE (1993) Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor. Nat Genet 5:95-100
228. Weiler R, Lassmann H, Fischer P, Jellinger K, Winkler H (1990) A high ratio of chromogranin A to synaptin/synaptophysin is a common feature of brains in Alzheimer and Pick disease. FEBS Lett 263:337-339
229. Yamazaki T, Selkoe DJ, Koo EH (1995) Trafficking of cell surface beta-amyloid precursor protein: Retrograde and transcytotic transport in cultured neurons. J Cell Biol 129:431-442
230. Yang G, Gong YD, Gong K, Jiang WL, Kwon E, Wang P, Zheng H, Zhang XF, Gan WB, Zhao NM (2005) Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2. Neurosci Lett 384:66-71
231. Yankner BA, Duffy LK, Kirschner DA (1990) Neurotrophic and neurotoxic effects of amyloid beta protein: Reversal by tachykinin neuropeptides. Science 250:279-282
232. Yao PJ, Morsch R, Callahan LM, Coleman PD (1999) Changes in synaptic expression of clathrin assembly protein AP180 in Alzheimer's disease analysed by immunohistochemistry. Neuroscience 94:389-394
233. Yao PJ, Zhu M, Pyun EI, Brooks AI, Therianos S, Meyers VE, Coleman PD (2003) Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease. Neurobiol Dis 12(2):97-109
234. Zampieri N, Xu CF, Neubert TA, Chao MV (2005) Cleavage of p75 neurotrophin receptor by alpha-secretase and gamma-secretase requires specific receptor domains. J Biol Chem 280:14563-14571
235. Zhan SS, Beyreuther K, Schmitt HP (1993) Quantitative assessment of the synaptophysin immuno-reactivity of the cortical neuropil in various neurodegenerative disorders with dementia. Dementia 4:66-74
236. Zhan SS, Beyreuther K, Schmitt HP (1994) Synaptophysin immunoreactivity of the cortical neuropil in vascular dementia of Binswanger type compared with the dementia of Alzheimer type and nondemented controls. Dementia 5:79-87
237. Zheng H, Jiang M, Trumbauer ME, Sirinathsinghji DJ, Hopkins R, Smith DW, Heavens RP, Dawson GR, Boyce S, Conner MW, Stevens KA, Slunt HH, Sisoda SS, Chen HY, Van der Ploeg LH (1995) Beta-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81:525-531
238. Zubenko GS, Kopp U, Seto T, Firestone LL (1999) Platelet membrane fluidity individuals at risk for Alzheimer's disease: A comparison of results from fluorescence spectroscopy and electron spin resonance spectroscopy. Psychopharmacology (Berl.) 145:175-180