Variations in the neuropathology of familial Alzheimer's disease

Acta Neuropathologica

Volumn 118, Issue 1, 2009, Pages 37-52

  Shepherd, Claire ^a,b   McCann, Heather ^a,b   Halliday, Glenda Margaret ^a,b  

^a NEUROSCIENCE RESEARCH AUSTRALIA   (Australia)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

Author keywords

Alzheimer's disease; Amyloid precursor protein; Familial; Neuropathology; Presenilin

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; PRESENILIN 1; PRESENILIN 2; TAU PROTEIN;

ALZHEIMER DISEASE; AUTOSOMAL DOMINANT DISORDER; BRAIN ATROPHY; CELL LOSS; CEREBROVASCULAR DISEASE; FAMILIAL DISEASE; GENE MUTATION; GENETIC ASSOCIATION; HUMAN; INFLAMMATION; NEUROFIBRILLARY TANGLE; NEUROPATHOLOGY; NEUROTOXICITY; ONSET AGE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; REVIEW; TAUOPATHY; VASCULAR AMYLOIDOSIS;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; ANIMALS; ATROPHY; BRAIN; CELL DEATH; HUMANS; NEUROIMMUNOMODULATION; NEURONS; PHOSPHORYLATION; PRESENILINS; SENILE PLAQUES; TAU PROTEINS; TAUOPATHIES;

EID: 67349158815     PISSN: 00016322     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00401-009-0521-4     Document Type: Review

References (231)

1. Ahn KW, Joo Y, Choi Y et al (2008) Swedish amyloid precursor protein mutation increases cell cycle-related proteins in vitro and in vivo. J Neurosci Res 86(11):2476-2487
2. Albani D, Roiter I, Artuso V et al (2007) Presenilin-1 mutation E318G familial Alzheimer's disease in the Italian population. Neurobiol Aging 28:1682-1688
3. Alonso AC, Li B, Grundke-Iqbal I, Iqbal K (2008) Mechanism of tau-induced neurodegeneration in Alzheimer disease and related tauopathies. Curr Alzheimer Res 5(4):375-384
4. Alonso AC, Zaidi T, Grundke-Iqbal I, Iqbal K (1994) Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proc Natl Acad Sci USA 91(12):5562-5566
5. Alvarez A, Munoz JP, Maccioni RB (2001) A Cdk5-p35 stable complex is involved in the beta-amyloid-induced deregulation of cdk5 activity in hippocampal neurons. Exp Cell Res 264(2):266-274
6. Alvarez A, Toro R, Caceres A, Maccioni RB (1999) Inhibition of tau phosphorylating protein kinase cdk5 prevents beta-amyloid-induced neuronal death. FEBS Lett 459(3):421-426
7. Arendt T, Holzer M, Gertz HJ, Bruckner MK (1999) Cortical load of PHF-tau in Alzheimer's disease is correlated to cholinergic dysfunction. J Neural Transm 106(5-6):513-523
8. Augustinack JC, Schneider A, Mandelkow EM, Hyman BT (2002) Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. Acta Neuropathol 103(1):26-35
9. Baki L, Neve R, Shao Z et al (2008) Wild-type but not FAD mutant presenilin-1 prevents neuronal degeneration by promoting phosphatidylinositol 3-kinase neuroprotective signaling. J Neurosci 28(2):483-490
10. Baki L, Shioi J, Wen P et al (2004) PS1 activates PI3 K thus inhibiting GSK-3 activity and tau overphosphorylation: Effects of FAD mutations. EMBO J 23(13):2586-2596
11. Basun H, Bogdanovic N, Ingelsson M et al (2008) Clinical and neuropathological features of the arctic APP gene mutation causing early-onset Alzheimer disease. Arch Neurol 65(4):499-505
12. Batelli S, Albani D, Prato F et al (2008) Early-onset Alzheimer disease in an Italian family with presenilin-1 double mutation E318G and G394 V. Alzheimer Dis Assoc Disord 22(2):184-187
13. Beglopoulos V, Sun X, Saura C et al (2004) Reduced B-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice. J Biol Chem 279(45):46907-46914
14. Bentahir M, Nyabi O, Verhamme J et al (2006) Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J Neurochem 96(3):732-742
15. Benzing WC, Ikonomovic MD, Brady DR, Mufson EJ, Armstrong DM (1993) Evidence that transmitter-containing dystrophic neurites precede paired helical filament and Alz-50 formation within senile plaques in the amygdala of nondemented elderly and patients with Alzheimer's disease. J Comp Neurol 334(2):176-191
16. Bergman ALH, Winblad B, Lundkvist J, Näslund J (2004) The extreme C terminus of presenilin 1 is essential for gamma-secretase complex assembly and activity. J Biol Chem 279(44):45564-45572
17. Bitan G, Kirkitadze MD, Lomakin A et al (2003) Amyloid beta-protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways. Proc Natl Acad Sci USA 100(1):330-335
18. Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer's disease. Lancet 368(9533):387-403
19. Bobinski M, Wegiel J, Tarnawski M et al (1997) Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease. J Neuropathol Exp Neurol 56(4):414-420
20. Bobinski M, Wegiel J, Wisniewski HM et al (1995) Atrophy of hippocampal formation subdivisions with stage and duration of Alzheimer's disease. Dementia 6:205-210
21. Bogdanovic N, Zilmer M, Zilmer K, Rehema A, Karelson E (2001) The Swedish APP670/671 Alzheimer's disease mutation: The first evidence for strikingly increased oxidative injury in the temporal inferior cortex. Dement Geriatr Cogn Disord 12(6):364-370
22. Borchelt D, Thinakaran G, Eckman C et al (1996) Familial Alzheimer's disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 17:1005-1013
23. Bornebroek M, Haan J, Maat-Schieman ML, Van Duinen SG, Roos RA (1996) Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): I - a review of clinical, radiologic and genetic aspects. Brain Pathol 6(2):111-114
24. Boutajangout A, Boom A, Leroy K, Brion JP (2004) Expression of tau mRNA and soluble tau isoforms in affected and non-affected brain areas in Alzheimer's disease. FEBS Lett 576(1-2):183-189
25. Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 112(4):389-404
26. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239-259
27. Braak H, Braak E, Grundke-Iqbal I, Iqbal K (1986) Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: A third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett 65(3):351-355
28. Bramblett GT, Trojanowski JQ, Lee VM (1992) Regions with abundant neurofibrillary pathology in human brain exhibit a selective reduction in levels of binding-competent tau and accumulation of abnormal tau-isoforms (A68 proteins). Lab Invest 66(2):212-222
29. Broe M, Shepherd CE, Milward EA, Halliday GM (2001) Relationship between DNA fragmentation, morphological changes and neuronal loss in Alzheimer's disease and dementia with Lewy bodies. Acta Neuropathol 101(6):616-624
30. Brooks WS, Kwok JB, Halliday GM et al (2004) Hemorrhage is uncommon in new Alzheimer family with Flemish amyloid precursor protein mutation. Neurology 63(9):1613-1617
31. Brooks WS, Kwok JB, Kril JJ et al (2003) Alzheimer's disease with spastic paraparesis and 'cotton wool' plaques: Two pedigrees with PS-1 exon 9 deletions. Brain 126(Pt 4):783-791
32. Brunkan AL, Martinez M, Wang J et al (2005) Two domains within the first putative transmembrane domain of presenilin 1 differentially influence presenilinase and gamma-secretase activity. J Neurochem 94(5):1315-1328
33. Butterfield DA, Castegna A, Lauderback CM, Drake J (2002) Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death. Neurobiol Aging 23(5):655-664
34. Cagnin A, Gerhard A, Banati R (2002) In vivo imaging of neuroinflammation. Eur Neuropsychopharmacol 12(6):581-586
35. Chan D, Fox NC, Scahill RI et al (2001) Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease. Ann Neurol 49(4):433-442
36. Chan S, Culmsee C, Haughey N, Klapper W, Mattson M (2002) Presenilin-1 mutations sensitize neurons to DNA damage-induced death by a mechanism involving perturbed calcium homeostasis and activation of calpains and caspase-12. Neurobiol Dis 11(1):2-19
37. Chen F, Gu Y, Hasegawa H et al (2002) Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch. J Biol Chem 277(39):36521-36526
38. Citron M, Oltersdorf T, Haas C (1992) Mutation of the β-Amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature 360:672-674
39. Cotman CW, Poon WW, Rissman RA, Blurton-Jones M (2005) The role of caspase cleavage of tau in Alzheimer disease neuropathology. J Neuropathol Exp Neurol 64(2):104-112
40. Cotman CW, Su JH (1996) Mechanisms of neuronal death in Alzheimer's disease. Brain Pathol 6:493-506
41. Cotman CW, Whittemore ER, Watt JA, Anderson AJ, Loo DT (1994) Possible role of apoptosis in Alzheimer's disease. Ann N Y Acad Sci 747:36-49
42. Cras P, van Harskamp F, Hendriks L et al (1998) Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala→Gly mutation. Acta Neuropathol 96(3):253-260
43. Crook R, Verkkoniemi A, Perez-Tur J et al (1998) A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1. Nat Med 4(4):452-455
44. Crouch PJ, Harding SM, White AR et al (2008) Mechanisms of A beta mediated neurodegeneration in Alzheimer's disease. Int J Biochem Cell Biol 40(2):181-198
45. De Felice FG, Wu D, Lambert MP et al (2008) Alzheimer's disease-type neuronal tau hyperphosphorylation induced by A-beta oligomers. Neurobiol Aging 29(9):1334-1347
46. De Strooper B, Annaert W, Cupers P et al (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398(6727):518-522
47. De Strooper B, Saftig P, Craessaerts K et al (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391(6665):387-390
48. Dermaut B, Kumar-Singh S, De Jonghe C et al (2001) Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's disease due to a novel presenilin 1 mutation. Brain 124(Pt 12):2383-2392
49. Dermaut B, Kumar-Singh S, Engelborghs S et al (2004) A novel presenilin 1 mutation associated with Pick's disease but not β-amyloid plaques. Ann Neurol 55(5):617-626
50. Deshpande A, Mina E, Glabe C, Busciglio J (2006) Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons. J Neurosci 26(22):6011-6018
51. Dowjat W, Kuchna I, Wisniewski T, Weigel J (2004) A novel highly pathogenic Alzheimer presenilin 1 mutation in codon 117 (Pro117Ser): comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations. J Alzheimer's Dis 6(1):31-43
52. Dumanchin C, Tournier I, Martin C et al (2006) Biological effects of four PSEN1 gene mutations causing Alzheimer disease with spastic paraparesis and cotton wool plaques. Hum Mutat 27(10):1063-1071
53. Eckert A, Marques CA, Keil U, Schussel K, Muller WE (2003) Increased apoptotic cell death in sporadic and genetic Alzheimer's disease. Ann N Y Acad Sci 1010:604-609
54. Eckert A, Steiner B, Marques C et al (2001) Elevated vulnerability to oxidative stress-induced cell death and activation of caspase-3 by the Swedish amyloid precursor protein mutation. J Neurosci Res 64(2):183-192
55. Eikelenboom P, Veerhuis R (1996) The role of complement and activated microglia in the pathogenesis of Alzheimer's disease. Neurobiol Aging 17:673-680
56. Esch FS, Keim PS, Beattie EC et al (1990) Cleavage of amyloid beta peptide during constitutive processing of its precursor. Science 248(4959):1122-1124
57. Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL (2005) Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology 64(6):1032-1039
58. Fox NC, Cousens S, Scahill R, Harvey RJ, Rossor MN (2000) Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: Power calculations and estimates of sample size to detect treatment effects. Arch Neurol 57(3):339-344
59. Frackowiak J, Wisniewski HM, Wegiel J et al (1992) Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils. Acta Neuropathol 84(3):225-233
60. Gahtan E, Overmier JB (1999) Inflammatory pathogenesis in Alzheimer's disease: Biological mechanisms and cognitive sequeli. Neurosci Biobehav Rev 23(5):615-633
61. Giliberto L, Zhou D, Weldon R et al (2008) Evidence that the Amyloid beta Precursor Protein-intracellular domain lowers the stress threshold of neurons and has a "regulated" transcriptional role. Mol Neurodegen 3:12-23
62. Goate A, Chartierharlin MC, Mullan M et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's-disease. Nature 349:704-706
63. Gomez-Isla T, Growdon W, McNamara M et al (1999) The impact of different presenilin 1 and presenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain. Evidence for other phenotype-modifying factors. Brain 122:1709-1719
64. Gómez-Isla T, Wasco W, Pettingell WP et al (1997) A novel presenilin-1 mutation: Increased β-amyloid and neurofibrillary changes. Ann Neurol 41:809-813
65. Gomez-Ramos A, Diaz-Hernandez M, Cuadros R, Hernandez R, Avila J (2006) Extracellular tau is toxic to neuronal cells. FEBS Lett 580:4842-4850
66. Gordon M, Holcomb L, Jantzen P et al (2002) Time course of the development of Alzheimer-like pathology in the doubly transgenic PS1+APP mouse. Exp Neurol 173(2):183-195
67. Grabowski TJ, Cho HS, Vonsattel JP, Rebeck GW, Greenberg SM (2001) Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy. Ann Neurol 49(6):697-705
68. Gregory G, Macdonald V, Schofield P, Kril J, Halliday G (2006) Differences in regional brain atrophy in genetic forms of Alzheimer's disease. Neurobiol Aging 27(3):387-393
69. Gregory GC, Halliday GM (2005) What is the dominant Abeta species in human brain tissue? A review. Neurotox Res 7(1-2):29-41
70. Haass C, Hung AY, Vigo-Pelfrey C et al (1992) Amyloid b-peptide is produced by cultured cells during normal metabolism. Nature 359:322-327
71. Haass C, Selkoe DJ (1993) Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide. Cell 75:1039-1042
72. Haleem K, Lippa CF, Smith TW et al (2007) Presenilin-1 C410Y Alzheimer disease plaques contain synaptic proteins. Am J Alzheimer's Dis Other Dementias 22(2):137-144
73. Halliday GM, Double KL, Macdonald V, Kril JJ (2003) Identifying severely atrophic cortical subregions in Alzheimer's disease. Neurobiol Aging 24(6):797-806
74. Hanger DP, Brion JP, Gallo JM et al (1991) Tau in Alzheimer's disease and Down's syndrome is insoluble and abnormally phosphorylated. Biochem J 275(Pt 1):99-104
75. Hardy J, Higgins G (1992) Alzheimer's disease: The amyloid cascade hypothesis. Science 256:184-185
76. Harper JD, Wong SS, Lieber CM, Lansbury PT (1997) Observation of metastable Abeta amyloid protofibrils by atomic force microscopy. Chem Biol 4(2):119-125
77. Hartley DM, Walsh DM, Ye CP et al (1999) Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J Neurosci 19(20):8876-8884
78. Hashimoto Y, Niikura T, Ito Y, Nishimoto I (2000) Multiple mechanisms underlie neurotoxicity by different types of Alzheimer's disease mutations of amyloid precursor protein. J Biol Chem 275(44):34541-34551
79. Heckmann J, Low W, de Villers C et al (2004) Novel presenilin 1 mutation with profound neurofibrillay pathology in an indigenous Southern African family with early-onset Alzheimer's disease. Brain 127(1):133-142
80. Hendrie HC (1998) Epidemiology of dementia and Alzheimer's disease. Am J Geriatr Psychiatry 6(2 Suppl 1):S3-S18
81. Herreman A, Serneels L, Annaert W et al (2000) Total inactivation of gamma-secretase activity in presenilin-deficient embryonic stem cells. Nature Cell Biol 2:461-462
82. Herrmann M, Golombowski S, Krauchi K et al (1999) ELISA-quantitation of phosphorylated tau protein in the Alzheimer's disease brain. Eur Neurol 42(4):205-210
83. Houlden H, Baker M, McGowan E et al (2000) Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations. Ann Neurol 48(5):806-808
84. Iadecola C, Zhang F, Niwa K et al (1999) SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat Neurosci 2(2):157-161
85. Ingelsson M, Fukumoto H, Newell KL et al (2004) Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology 62(6):925-931
86. Iqbal K, Alonso Adel C, Grundke-Iqbal I (2008) Cytosolic abnormally hyperphosphorylated tau but not paired helical filaments sequester normal MAPs and inhibit microtubule assembly. J Alzheimer's Dis 14(4):365-370
87. Iqbal K, Grundke-Iqbal I (1997) Elevated levels of tau and ubiquitin in brain and cerebrospinal fluid in Alzheimer's disease. Int Psychogeriatr 9(1):289-296
88. Ishii K, Ii K, Hasegawa T et al (1997) Increased Aβ 42(43)-plaque deposition in early-onset familial Alzheimer's disease brains with the deletion of exon 9 and the missense point mutation (H163R) in the PS-1 gene. Neurosci Lett 228:17-20
89. Ishii K, Lippa C, Tomiyama T et al (2001) Distinguishable effects of presenilin-1 and APP717 mutations on amyloid plaque deposition. Neurobiol Aging 22:367-376
90. Iwatsubo T, Odaka A, Suzuki N et al (1994) Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: Evidence that an initially deposited species is A beta 42(43). Neuron 13(1):45-53
91. Jack CR Jr, Petersen RC, Xu Y et al (2000) Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology 55(4):484-489
92. Jellinger KA (2009) Criteria for the neuropathological diagnosis of dementing disorders: Routes out of the swamp? Acta Neuropathol 117(2):101-110
93. Jobst KA, Smith AD, Szatmari M et al (1994) Rapidly progressing atrophy of medial temporal lobe in Alzheimer's disease. Lancet 343(8901):829-830
94. Jost BC, Grossberg GT (1995) The natural history of Alzheimer's disease: a brain bank study. J Am Geriatr Soc 43(11):1248-1255
95. Kalaria DL, Cohen DL, Premkumar DRD (1996) Cellular aspects of the inflammatory response in Alzheimer's disease. Neurodegeneration 5:497-503
96. Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS (2001) Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 414(6864):643-648
97. Karlstrom H, Brooks WS, Kwok JB et al (2008) Variable phenotype of Alzheimer's disease with spastic paraparesis. J Neurochem 104(3):573-583
98. Kayed R, Sokolov Y, Edmonds B et al (2004) Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein misfolding diseases. J Biol Chem 279(45):46363-46366
99. Keil U, Hauptmann S, Bonert A et al (2006) Mitochondrial dysfunction induced by disease relevant AbetaPP and tau protein mutations. J Alzheimers Dis 9(2):139-146
100. Khatoon S, Grundke-Iqbal I, Iqbal K (1994) Levels of normal and abnormally phosphorylated tau in different cellular and regional compartments of Alzheimer disease and control brains. FEBS Lett 351(1):80-84
101. Kim DY, Ingano LA, Kovacs DM (2002) Nectin-1alpha, an immunoglobulin-like receptor involved in the formation of synapses, is a substrate for presenilin/gamma-secretase-like cleavage. J Biol Chem 277(51):49976-49981
102. Kim HS, Kim EM, Lee JP et al (2003) C-terminal fragments of amyloid precursor protein exert neurotoxicity by inducing glycogen synthase kinase-3beta expression. FASEB J 17(13):1951-1953
103. Klein WL, Stine WB Jr, Teplow DB (2004) Small assemblies of unmodified amyloid beta-protein are the proximate neurotoxin in Alzheimer's disease. Neurobiol Aging 25(5):569-580
104. Kobayashi K, Nakano H, Hayashi M et al (2003) Association of phosphorylation site of tau protein with neuronal apoptosis in Alzheimer's disease. J Neurol Sci 208(1-2):17-24
105. Kril J, Hodges J, Halliday G (2004) Relationship between hippocampal volume and CA1 neuron loss in brains of humans with and without Alzheimer's disease. Neurosci Lett 361(1-3):9-12
106. Kril J, Patel S, Harding A, Halliday G (2002) Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation. Acta Neuropathol 103(4):370-376
107. Kumar-Singh S, Cras P, Wang R et al (2002) Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric. Am J Pathol 161(2):507-520
108. Kumar-Singh S, Theuns J, Van Broeck B et al (2006) Mean age of onset of familial Alzheimer's disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40. Hum Mutat 27(7):686-695
109. Kurt M, Davies D, Kidd M et al (2001) Neurodegenerative changes associated with beta-amyloid deposition in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes. Exp Neurol 171:59-71
110. Kwok JB, Halliday GM, Brooks WS et al (2003) Presenilin-1 mutation L271 V results in altered exon 8 splicing and Alzheimer's disease with non-cored plaques and no neuritic dystrophy. J Biol Chem 278(9):6748-6754
111. Lacor PN, Buniel MC, Chang L et al (2004) Synaptic targeting by Alzheimer's-related amyloid beta oligomers. J Neurosci 24(45):10191-10200
112. Lacor PN, Buniel MC, Furlow PW et al (2007) Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J Neurosci 27(4):796-807
113. Lai RY, Gertz HN, Wischik DJ et al (1995) Examination of phosphorylated tau protein as a PHF-precursor at early stage Alzheimer's disease. Neurobiol Aging 16(3):433-445
114. Lambert MP, Barlow AK, Chromy BA et al (1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA 95(11):6448-6453
115. Lammich S, Okochi M, Takeda M et al (2002) Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide. J Biol Chem 277(47):44754-44759
116. Lantos PL, Luthert PJ, Hanger D et al (1992) Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology. Neurosci Lett 137(2):221-224
117. Lazarov O, Morfini GA, Pigino G et al (2007) Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1. J Neurosci 27(26):7011-7020
118. Le T, Crook R, Hardy J, Dickson D (2001) Cotton wool plaques in non-familial late-onset Alzheimer's disease. J Neuropathol Exp Neurol 60(11):1051-1061
119. Ledesma MD, Avila J, Correas I (1995) Isolation of a phosphorylated soluble tau fraction from Alzheimer's disease brain. Neurobiol Aging 16(4):515-522
120. Lewandowska E, Bertrand E, Kulczycki J et al (1999) Microglia and neuritic plaques in familial Alzheimer's disease induced by a new mutation of presenilin-1 gene. An ultrastructural study. Folia Neuropathol 37(4):243-246
121. Lin H, Bhatia R, Lal R (2001) Amyloid beta protein forms ion channels: implications for Alzheimer's disease pathophysiology. FASEB J 15(13):2433-2444
122. Lippa CF, Saunders AM, Smith TW et al (1996) Familial and sporadic Alzheimer's disease: Neuropathology cannot exclude a final common pathway. Neurology 46:406-412
123. Lucas JJ, Hernandez F, Gomez-Ramos P et al (2001) Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J 20(1-2):27-39
124. Lue LF, Kuo YM, Roher AE et al (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol 155(3):853-862
125. Malik B, Currais A, Andres A et al (2008) Loss of neuronal cell cycle control as a mechanism of neurodegeneration in the presenilin-1 Alzheimer's disease brain. Cell cycle 7(5):637-646
126. Mandelkow E, von Bergen M, Biernat J, Mandelkow EM (2007) Structural principles of tau and the paired helical filaments of Alzheimer's disease. Brain Pathol 17(1):83-90
127. Mann D, Iwatsubo T, Nochlin D et al (1997) Amyloid (Abeta) deposition in chromosome 1-linked Alzheimer's disease: The Volga German families. Ann Neurol 41(1):52-57
128. Mann D, Pickering-Brown S, Takeuchi A, Iwatsubo T, F.A.s.D.P.S. Group (2001) Amyloid angiopathy and variability in amyloid B deposition is determined by mutation position in presenilin-1-linked Alzheimer's disease. Am J Pathol 158(6):2165-2175
129. Mann D, Takeuchi A, Sato S et al (2001) Cases of Alzheimer's disease due to deletion of exon 9 of the presenilin-1 gene show an unusual but characteristic B-amyloid pathology known as 'cotton wool' plaques. Neuropathol Appl Neurobiol 27:189-196
130. Mann DM, Iwatsubo T, Cairns NJ et al (1996) Amyloid beta protein (Abeta) deposition in chromosome 14-linked Alzheimer's disease: Predominance of Abeta42(43). Ann Neurol 40:149-156
131. Mann DMA, Iwatsubo T, Ihara Y et al (1996) Predominant deposition of amyloid-beta(42(43)) in plaques in cases of Alzheimer's-disease and hereditary cerebral-haemorrhage associated with mutations in the amyloid precursor protein gene. Am J Pathol 148:1257-1266
132. Marambaud P, Shioi J, Serban G et al (2002) A presenilin-1/ gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J 21(8):1948-1956
133. Masliah E, Mallory M, Alford M, Tanaka S, Hansen LA (1998) Caspase dependent DNA fragmentation might be associated with excitotoxicity in Alzheimer disease. J Neuropathol Exp Neurol 57(11):1041-1052
134. Mattson M, Chan S, Camandola S (2001) Presenilin mutations and calcium signaling defects in the nervous and immune systems. Bioessays 23:733-744
135. McLean CA, Cherny RA, Fraser FW et al (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 46(6):860-866
136. Miklossy J, Taddei K, Suva D et al (2003) Two novel presenilin-1 mutations (Y256S and Q222H) are associated with early-onset Alzheimer's disease. Neurobiol Aging 24(5):655-662
137. Miravalle L, Calero M, Takao M et al (2005) Amino-terminally truncated Abeta peptide species are the main component of cotton wool plaques. Biochemistry 44(32):10810-10821
138. Mirra SS, Heyman A, McKeel D et al (1991) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41(4):479-486
139. Moehlmann T, Winkler E, Xia X et al (2002) Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production. Proc Natl Acad Sci USA 99(12):8025-8030
140. Mukaetova-Ladinska EB, Garcia-Siera F, Hurt J et al (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
141. Mukaetova-Ladinska EB, Harrington CR, Roth M, Wischik CM (1993) Biochemical and anatomical redistribution of tau protein in Alzheimer's disease. Am J Pathol 143:565-578
142. Muller T, Meyer HE, Egensperger R, Marcus K (2008) The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-relevance for Alzheimer's disease. Prog Neurobiol 85(4):393-406
143. Munch G, Gasic-Milenkovic J, Dukic-Stefanovic S et al (2003) Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells. Exp Brain Res 150(1):1-8
144. Munch G, Shepherd C, McCann H et al (2002) Intraneuronal advanced glycation endproducts in presenilin-1 Alzheimer's disease. Neuroreport 13(5):601-604
145. Murakami D, Okamoto I, Nagano O et al (2003) Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44. Oncogene 22(10):1511-1516
146. Nagele RG, D'Andrea MR, Lee H, Venkataraman V, Wang HY (2003) Astrocytes accumulate A beta 42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res 971(2):197-209
147. Nagy Z (2000) Cell cycle regulatory failure in neurones: Causes and consequences. Neurobiol Aging 21(6):761-769
148. Nakayama K, Ohkawara T, Hiratochi M, Koh CS, Nagase H (2008) The intracellular domain of amyloid precursor protein induces neuron-specific apoptosis. Neurosci Lett 444(2):127-131
149. Naslund J, Schierhorn A, Hellman U et al (1994) Relative abundance of Alzheimer A beta amyloid peptide variants in Alzheimer disease and normal aging. Proc Natl Acad Sci USA 91(18):8378-8382
150. Natte R, Maat-Schieman ML, Haan J et al (2001) Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type is associated with cerebral amyloid angiopathy but is independent of plaques and neurofibrillary tangles. Ann Neurol 50(6):765-772
151. Nilsberth C, Westlind-Danielsson A, Eckman CB et al (2001) The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nature Neurosci 4(9):887-893
152. Nochlin D, Bird TD, Nemens EJ, Ball MJ, Sumi SM (1998) Amyloid angiopathy in a Volga German family with Alzheimer's disease and a presenilin-2 mutation (N141I). Ann Neurol 43(1):131-135
153. Nochlin D, van Belle G, Bird TD, Sumi SM (1993) Comparison of the severity of neuropathologic changes in familial and sporadic Alzheimer's disease. Alzheimer Dis Assoc Disord 7(4):212-222
154. Nunomura A, Chiba S, Lippa CF et al (2004) Neuronal RNA oxidation is a prominent feature of familial Alzheimer's disease. Neurobiol Dis 17(1):108-113
155. Oddo S, Vasilevko V, Caccamo A et al (2006) Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J Biol Chem 281(51):39413-39423
156. Parachikova A, Agadjanyan M, Cribbs D et al (2006) Inflammatory changes parallel the early stages of Alzheimer disease. Neurobiol Aging 28(12):1821-1833
157. Paradis E, Douillard H, Koutroumanis M, Goodyer C, LeBlanc A (1996) Amyloid beta peptide of Alzheimer's disease downregulates Bcl-2 and upregulates bax expression in human neurons. J Neurosci 16(23):7533-7539
158. Paresce D, Chung H, Maxfield F (1997) Slow degradation of aggregates of the Alzheimer's disease amyloidB-protein by microglial cells. J Biol Chem 272:29390-29397
159. Park S, Ferriera A (2005) The generation of a 17 kDa neurotoxic fragment: And alternative mechanism by which tau mediates beta-amyloid induced neurodegeneration. J Neurosci 25:5365-5375
160. Patel N, Paris D, Mathurs V et al (2005) Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease. J Neuroinflamm 2(1):9-18
161. Pigino G, Pelsman A, Mori H, Busciglio J (2001) Presenilin-1 mutations reduce cytoskeletal association, deregulate neurite growth, and potentiate neuronal dystrophy and tau phosphorylation. J Neurosci 21(3):834-842
162. Piguet O, Double KL, Kril JJ et al (2007) White matter loss in healthy aging: A postmortem analysis. Neurobiol Aging. doi: 10.1016/ j.neurobiolaging.2007.10.015 [Epub ahead of print]
163. Raber J, Huang Y, Ashford JW (2004) ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol Aging 25(5):641-650
164. Raux G, Gantier R, Thomas-Anterion C et al (2000) Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology 55(10):1577-1578
165. Rogers J, Luber-Narod J, Styren SD, Civin WH (1988) Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer's disease. Neurobiol Aging 9:339-349
166. Rossi G, Giaccone G, Maletta R et al (2004) A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene. Neurology 63(5):910-912
167. Rossler M, Zarski R, Bohl J, Ohm TG (2002) Stage-dependent and sector-specific neuronal loss in hippocampus during Alzheimer's disease. Acta Neuropathol 103(4):363-369
168. Rossner S, Lange-Dohna C, Zeitschel U, Perez-Polo JR (2005) Alzheimer's disease beta-secretase BACE1 is not a neuron-specific enzyme. J Neurochem 92(2):226-234
169. Rossner S, Sastre M, Bourne K, Lichtenthaler SF (2006) Transcriptional and translational regulation of BACE1 expression - implications for Alzheimer's disease. Prog Neurobiol 79(2):95-111
170. Rovelet-Lecrux A, Frebourg T, Tuominen H et al (2007) APP locus duplication in a Finnish family with dementia and intracerebral haemorrhage. J Neurol Neurosurg Psychiatry 78(10):1158-1159
171. Rovelet-Lecrux AHD, Raux G, Le Meur N, Laquerrière A, Vital A,
172. Saitoh T, Sundsmo M, Roch JM et al (1989) Secreted form of amyloid beta protein precursor is involved in the growth regulation of fibroblasts. Cell 58(4):615-622
173. Sastre M, Steiner H, Fuchs K et al (2001) Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch. EMBO Rep 2(9):835-841
174. Saura CA, Choi SY, Beglopoulos V et al (2004) Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42(1):23-36
175. Schindowski K, Belarbi K, Buee L (2008) Neurotrophic factors in Alzheimer's disease: Role of axonal transport. Genes Brain Behav 7(1):43-56
176. Schroeter EH, Ilagan MX, Brunkan AL et al (2003) A presenilin dimer at the core of the gamma-secretase enzyme: Insights from parallel analysis of Notch 1 and APP proteolysis. Proc Natl Acad Sci USA 100(22):13075-13080
177. Selkoe D, Kopan R (2003) Notch and Presenilin: Regulated intramembrane proteolysis links development and degeneration. Ann Rev Neurosci 26:565-597
178. Seubert P, Oltersdorf T, Lee MG et al (1993) Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide. Nature 361(6409):260-263
179. Shankar GM, Bloodgood BL, Townsend M et al (2007) Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci 27(11):2866-2875
180. Sheng JG, Mrak RE, Griffin WS (1997) Neuritic plaque evolution in Alzheimer's disease is accompanied by transition of activated microglia from primed to enlarged to phagocytic forms. Acta Neuropathol 94(1):1-5
181. Shepherd C, Grace E, Mann D, Halliday G (2007) Relationship between neuronal loss and 'inflammatory plaques' in early onset Alzheimer's disease. Neuropathol Appl Neurobiol 33(3):328-333
182. Shepherd C, Gregory G, Vickers J et al (2004) Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques. Neurobiol Dis 15(1):115-119
183. Shepherd CE, Gregory GC, Vickers JC, Halliday GM (2005) Novel 'inflammatory plaque' pathology in presenilin-1 Alzheimer's disease. Neuropathol Appl Neurobiol 31(5):503-511
184. Shepherd CE, Thiel E, McCann H, Harding TJ, Halliday GM (2000) Cortical Inflammation in Alzheimer's disease but not dementia with Lewy bodies. Arch Neurol 57:817-822
185. Shioi J, Georgakopoulos A, Mehta P et al (2007) FAD mutants unable to increase neurotoxic Abeta 42 suggest that mutation effects on neurodegeneration may be independent of effects on Abeta. J Neurochem 101(3):674-681
186. Shrimpton AE, Schelper RL, Linke RP et al (2007) A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease, seizures and cotton wool plaques, but not spastic paraparesis. Neuropathology 27(3):228-232
187. Sisodia SS, Koo EH, Beyreuther K, Unterbeck A, Price DL (1990) Evidence that beta-amyloid protein in Alzheimer's disease is not derived by normal processing. Science 248(4954):492-495
188. Smith M, Kwok J, McLean C et al (2001) Variable phenotype of Alzheimer's disease with spastic paraparesis. Ann Neurol 49(1):125-129
189. Sokolova A, Hill MD, Rahimi F et al (2008) Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer's disease. Brain Pathol. doi: 10.1111/j.1750-3639.2008.00188.x [Epub ahead of print]
190. Spires T, Orne J, SantaCruz K et al (2006) Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy. Am J Pathol 168(5):1598-1607
191. Stadelmann C, Deckwerth TL, Srinivasan A et al (1999) Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer's disease. Evidence for apoptotic cell death. Am J Pathol 155(5):1459-1466
192. Steiner H, Revesz T, Neumann M et al (2001) A pathogenic presenilin-1 deletion causes abberant AB42 production in the absence of congiophilic amyloid plaques. J Biol Chem 276(10):7233-7239
193. Stenh C, Nilsberth C, Hammarback J et al (2002) The Arctic mutation interferes with processing of the amyloid precursor protein. Neuroreport 13(15):1857-1860
194. Stoothoff WH, Johnson GV (2005) Tau phosphorylation: Physiological and pathological consequences. Biochem Biophys Acta 1739(2-3):280-297
195. Su JH, Anderson AJ, Cummings BJ, Cotman CW (1994) Immunohistochemical evidence for apoptosis in Alzheimer's disease. Neuroreport 5(18):2529-2533
196. Su JH, Deng G, Cotman CW (1997) Bax protein expression is increased in Alzheimer's brain: Correlations with DNA damage, Bcl-2 expression, and brain pathology. J Neuropathol Exp Neurol 56(1):86-93
197. Sudo S, Shiozawa M, Cairns N, Wada Y (2005) Aberrant accentuation of neurofibrillary degeneration in the hippocampus of Alzheimer's disease with amyloid precursor protein 717 and presenilin-1 gene mutations. J Neurol Sci 234(1-2):55-65
198. Takao M, Ghetti B, Hayakawa I et al (2002) A novel mutation (G217D) in the Presenilin 1 gene (PSEN1) in a Japanese family: Presenile dementia and parkinsonism are associated with cotton wool plaques in the cortex and striatum. Acta Neuropathol 104(2):155-170
199. Takashima A, Murayama M, Murayama O et al (1998) Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau. Proc Natl Acad Sci USA 95(16):9637-9641
200. Tamaoka A, Fraser PE, Ishii K et al (1998) Amyloid-beta-protein isoforms in brain of subjects with PS1-linked, beta APP-linked and sporadic Alzheimer disease. Brain Res Mol Brain Res 56(1-2):178-185
201. Tamaoka A, Odaka A, Ishibashi Y et al (1994) APP717 missense mutation affects the ratio of amyloid beta protein species (A beta 1-42/43 and a beta 1-40) in familial Alzheimer's disease brain. J Biol Chem 269(52):32721-32724
202. Tamaoka A, Sawamura N, Odaka A et al (1995) Amyloid beta protein 1-42/43 (A beta 1-42/43) in cerebellar diffuse plaques: Enzyme-linked immunosorbent assay and immunocytochemical study. Brain Res 679(1):151-156
203. Thaker U, McDonagh A, Iwatsubo T et al (2003) Tau load is associated with apolipoprotein E genotype and the amount of amyloid B protein, AB40, in sporadic and familial Alzheimer's disease. Neuropathol Appl Neurobiol 29:35-44
204. Thal DR, Arendt T, Waldmann G et al (1998) Progression of neurofibrillary changes and PHF-tau in end-stage Alzheimer's disease is different from plaque and cortical microglial pathology. Neurobiol Aging 19(6):517-525
205. Thinakaran G, Parent AT (2004) Identification of the role of presenilins beyond Alzheimer's disease. Pharmacol Res 50(4):411-418
206. Turner PR, O'Connor K, Tate WP, Abraham WC (2003) Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 70(1):1-32
207. Uchihara T, Nakamura A, Nakayama H et al (2003) Triple immunofluorolabeling with two rabbit polyclonal antibodies and a mouse monoclonal antibody allowing three-dimensional analysis of cotton wool plaques in Alzheimer disease. J Histochem Cytochem 51(9):1201-1206
208. van de Nes JA, Nafe R, Schlote W (2008) Non-tau based neuronal degeneration in Alzheimer's disease - an immunocytochemical and quantitative study in the supragranular layers of the middle temporal neocortex. Brain Res 1213:152-165
209. Van Nostrand WE, Melchor JP, Cho HS, Greenberg SM, Rebeck GW (2001) Pathogenic effects of D23 N Iowa mutant amyloid beta-protein. J Biol Chem 276(35):32860-32866
210. Verdile G, Gnjec A, Miklossy J et al (2004) Protein markers for Alzheimer disease in the frontal cortex and cerebellum. Neurology 63(8):1385-1392
211. Verkkoniemi A, Kalimo H, Paetau A et al (2001) Variant Alzheimer disease with spastic paraparesis: Neuropathological phenotype. J Neuropathol Exp Neurol 60(5):483-492
212. von Bernhardi R (2007) Glial cell dysregulation: A new perspective on Alzheimer disease. Neurotox Res 12(4):215-232
213. Walker ES, Martinez M, Brunkan AL, Goate A (2005) Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios. J Neurochem 92(2):294-301
214. Walsh DM, Klyubin I, Fadeeva JV et al (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416(6880):535-539
215. Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB (1997) Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate. J Biol Chem 272(35):22364-22372
216. Wang H, Pasternak J, Kuo H et al (2002) Soluble oligomers of beta amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. Brain Res 924(2):133-140
217. Weaver CL, Espinoza M, Kress Y, Davies P (2000) Conformational change as one of the earliest alterations of tau in Alzheimer's disease. Neurobiol Aging 21(5):719-727
218. Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP Jr, Yaffe K (2005) Obesity in middle age and future risk of dementia: A 27 year longitudinal population based study. Br Med J 330(7504):1360
219. Whitmer RA, Gunderson EP, Quesenberry CP Jr, Zhou J, Yaffe K (2007) Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr Alzheimer Res 4(2):103-109
220. Whitmer RA, Gustafson DR, Barrett-Connor E et al (2008) Central obesity and increased risk of dementia more than three decades later. Neurology 71(14):1057-1064
221. Whitwell JL, Shiung MM, Przybelski SA et al (2008) MRI patterns of atrophy associated with progression to AD in amnestic mild cognitive impairment. Neurology 70(7):512-520
222. Wimo A, Jonsson L, Winblad B (2006) An estimate of the worldwide prevalence, direct costs of dementia in 2003. Dement Geriatr Cogn Disord 21(3):175-181
223. Wischik CM, Edwards PC, Lai RY et al (1995) Quantitative analysis of tau protein in paired helical filament preparations: Implications for the role of tau protein phosphorylation in PHF assembly in Alzheimer's disease. Neurobiol Aging 16(3):409-417
224. Wolfe MS (2007) When loss is gain: Reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking point on the role of presenilin mutations in Alzheimer disease. EMBO Rep 8(2):136-140
225. Woltjer RL, Cimino PJ, Boutte AM et al (2005) Proteomic determination of widespread detergent-insolubility including Abeta but not tau early in the pathogenesis of Alzheimer's disease. FASEB J 19(13):1923-1925
226. Woodhouse A, Shepherd C, Sokolova A et al (2008) Cytoskeletal alterations differentiate presenilin-1 and sporadic Alzheimer's disease. Acta Neuropathol 117(1):19-29
227. Wyss-Coray T (2006) Inflammation in Alzheimer disease: Driving force, bystander or beneficial response. Nat Med 12(9):1005-1015
228. Xu M, Lai MT, Huang Q et al (2002) Gamma-secretase: Characterization and implication for Alzheimer disease therapy. Neurobiol Aging 23(6):1023-1030
229. Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer's disease. J Neurosci 21(8):2661-2668
230. Yokota O, Terada S, Ishizu H et al (2003) Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: A clinicopathological study of four autopsy cases. Acta Neuropathol 106(4):348-356
231. Zhao G, Mao G, Tan J et al (2004) Identification of a new presenilin-dependent zeta-cleavage site within the transmembrane domain of amyloid precursor protein. J Biol Chem 279(49):50647-50650