Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice

Journal of Neuroscience

Volumn 26, Issue 19, 2006, Pages 5167-5179

  Esposito, Luke ^a,b   Raber, Jacob ^a,e   Kekonius, Lisa ^a,f   Yan, Fengrong ^a   Yu, Giu Qiu ^a   Bien Ly, Nga ^a   Puoliväli, Jukka ^a,g   Scearce Levie, Kimberly ^a   Masliah, Eliezer ^c   Mucke, Lennart ^a,b,d  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d GLADSTONE INSTITUTE OF NEUROLOGICAL DISEASE   (United States)

^e OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^f KAROLINSKA INSTITUTE   (Sweden)

^g Cerebricon Limited   (Finland)

Author keywords

Alzheimer's disease; Amyloid precursor protein; Behavior; Mitochondria; Superoxide dismutase 2; Transgenic mice

Indexed keywords

AMYLOID PRECURSOR PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MICROTUBULE ASSOCIATED PROTEIN 2; SUPEROXIDE DISMUTASE; CELL SURFACE RECEPTOR; MANGANESE SUPEROXIDE DISMUTASE; PROTEASE NEXINS;

ALZHEIMER DISEASE; AMYLOIDOSIS; ANIMAL EXPERIMENT; ARTICLE; BEHAVIOR; BRAIN; DEMENTIA; ENZYME ACTIVITY; GLIOSIS; MITOCHONDRION; MOUSE; NERVE DEGENERATION; NEUROPATHY; NONHUMAN; PRIORITY JOURNAL; ANIMAL; ENZYME ACTIVATION; ENZYMOLOGY; GENETICS; HUMAN; MENTAL DISEASE; METABOLISM; PATHOPHYSIOLOGY; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; ENZYME ACTIVATION; HUMANS; MENTAL DISORDERS; MICE; MICE, TRANSGENIC; MITOCHONDRIA; RECEPTORS, CELL SURFACE; SUPEROXIDE DISMUTASE;

EID: 33646922865     PISSN: 02706474     EISSN: 02706474     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.0482-06.2006     Document Type: Article

References (107)

1. Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG (2003) Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol 161:41-54.
2. Andreassen OA, Ferrante RJ, Klivenyi P, Klein AM, Shinobu LA, Epstein CJ, Beal MF (2000) Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis. Ann Neurol 47:447-455.
3. Andreassen OA, Ferrante RJ, Dedeoglu A, Albers DW, Klivenyi P, Carlson EJ, Epstein CJ, Beal MF (2001) Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. Exp Neurol 167:189-195.
4. Attems J (2005) Sporadic cerebral amyloid angiopathy: Pathology, clinical implications, and possible pathomechanisms. Acta Neuropathol (Berl) 110:345-359.
5. Aucoin JS, Jiang P, Aznavour N, Tong XK, Buttini M, Descarries L, Hamel E (2005) Selective cholinergic denervation, independent from oxidative stress, in a mouse model of Alzheimer's disease. Neuroscience 132:73-86.
6. Beal MF (2005) Mitochondria take center stage in aging and neurodegeneration. Ann Neurol 58:495-505.
7. Benice T, Rizk A, Kohama S, Pfankuch T, Raber J (2006) Sex-differences in age-related cognitive decline in C57BL/6J mice associated with increased brain microtubule-associated protein 2 and synaptophysin immunoreactivity. Neuroscience 137:413-423.
8. 35 and amyloid β-protein oligomerization. J Am Chem Soc 125:15359-15365.
9. Blanchard V, Moussaoui S, Czech C, Touchet N, Bonici B, Planche M, Canton T, Jedidi I, Gohin M, Wirths O, Bayer TA, Langui D, Duyckaerts C, Tremp G, Pradier L (2003) Time sequence of maturation of dystrophic neurites associated with Aβ deposits in APP/PS1 transgenic mice. Exp Neurol 184:247-263.
10. Braak H, Braak E (1997) Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 18:351-357.
11. Brendza RP, Bacskai BJ, Cirrito JR, Simmons KA, Skoch JM, Klunk WE, Mathis CA, Bales KR, Paul SM, Hyman BT, Holtzman DM (2005) Anti-Aβ antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice. J Clin Invest 115:428-433.
12. Busciglio J, Pelsman A, Wong C, Pigino G, Yuan M, Mori H, Yankner BA (2002) Altered metabolism of the amyloid β precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron 33:677-688.
13. Butterfield DA, Bush AI (2004) Alzheimer's amyloid β-peptide (1-42): Involvement of methionine residue 35 in the oxidative stress and neurotoxicity properties of this peptide. Neurobiol Aging 25:563-568.
14. Butterfield DA, Drake J, Pocernich C, Castegna A (2001) Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid β-peptide. Trends Mol Med 7:548-554.
15. -/- mice: isoform-specific effects on neurodegeneration. J Neurosci 19:4867-4880.
16. Calhoun ME, Burgermeister P, Phinney AL, Stalder M, Tolnay M, Weiderhold KH, Abramowski D, Sturchler-Pierrat C, Sommer B, Staufenbiel M, Jucker M (1999) Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid. Proc Natl Acad Sci USA 96:14088-14093.
17. Calon F, Lim G, Yang F, Morihara T, Teter B, Ubeda O, Rostaing P, Triller A, Salem Jr N, Ashe K, Frautschy S, Cole G (2004) Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron 43:633-645.
18. Cardoso SM, Santana I, Swerdlow RH, Oliveira CR (2004) Mitochondria dysfunction of Alzheimer's disease cybrids enhances Aβ toxicity. J Neurochem 89:1417-1426.
19. Castellani RJ, Smith MA, Perry G, Friedland RP (2004) Cerebral amyloid angiopathy: major contributor or decorative response to Alzheimer's disease pathogenesis. Neurobiol Aging 25:599-602.
20. Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, Gan L (2005) SIRT1 protects against microglia-dependent amyloid-β toxicity through inhibiting NF-κB signaling. J Biol Chem 280:40364-40374.
21. Chin J, Palop JJ, Puoliväli J, Massaro C, Bien-Ly N, Gerstein H, Scearce-Levie K, Masliah E, Mucke L (2005) Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci 25:9694-9703.
22. Christie R, Yamada M, Moskowitz M, Hyman B (2001) Structural and functional disruption of vascular smooth muscle cells in a transgenic mouse model of amyloid angiopathy. Am J Pathol 158:1065-1071.
23. Chung JA, Cummings JL (2000) Neurobehavioral and neuropsychiatric symptoms in Alzheimer's disease: characteristics and treatment. Neurol Clin 18:829-846.
24. Coskun PE, Beal MF, Wallace DC (2004) Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci USA 101:10726-10731.
25. 1-42. J Neurosci 25:672-679.
26. Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP (2004) Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci USA 101:2070-2075.
27. DeMattos RB, Bales KR, Cummins DJ, Dodart J-C, Paul SM, Holtzman DM (2001) Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 98:8850-8855.
28. Eckert A, Keil U, Marques CA, Bonert A, Frey C, Schussel K, Muller WE (2003) Mitochondrial dysfunction, apoptotic cell death, and Alzheimer's disease. Biochem Pharmacol 66:1627-1634.
29. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. J Am Med Assoc 278:1349-1356.
30. Fryer JD, Simmons K, Parsadanian M, Bales KR, Paul SM, Sullivan PM, Holtzman DM (2005) Humanapolipoprotein E4 alters the amyloid-β40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model. J Neurosci 25:2803-2810.
31. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F, Guido T, Hagopian S, Johnson-Wood K, Khan K, Lee M, Leibowitz P, Lieberburg I, Little S, Masliah E, McConlogue L, et al. (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 373:523-527.
32. García-Ruiz C, Colell A, Morales A, Kaplowitz N, Fernández-Checa JC (1995) Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-κB: studies with isolated mitochondria and rat hepatocytes. Mol Pharmacol 48:825-834.
33. Gardner PR, Raineri I, Epstein LB, White CW (1995) Superoxide radical and iron modulate aconitase activity in mammalian cells. J Biol Chem 270:13399-13405.
34. Geyer MA, McIlwain KL, Paylor R (2002) Mouse genetic models for prepulse inhibition: an early review. Mol Psychiatry 7:1039-1053.
35. Götz J, Streffer J, David D, Schild A, Hoerndli F, Pennanen L, Kurosinski P, Chen F (2004) Transgenic animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy. Mol Psychiatry 9:664-683.
36. Greenberg SM, Gurol ME, Rosand J, Smith EE (2004) Amyloid angiopathy-related vascular cognitive impairment. Stroke 35:2616-2619.
37. Halliwell B, Gutteridge JMC (1985) Free radicals in biology and medicine. Oxford: Clarendon.
38. Hansson CA, Frykman S, Farmery MR, Tjernberg LO, Nilsberth C, Pursglove SE, Ito A, Winblad B, Cowburn RF, Thyberg J, Ankarcrona M (2004) Nicastrin, presenilin, APH-1, and PEN-2 form active γ-secretase complexes in mitochondria. J Biol Chem 279:51654-51660.
39. Harper DG, Stopa EG, McKee AC, Satlin A, Fish D, Volicer L (2004) Dementia severity and Lewy bodies affect circadian rhythms in Alzheimer disease. Neurobiol Aging 25:771-781.
40. Hatfield CF, Herbert J, van Someren EJ, Hodges JR, Hastings MH (2004) Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer's dementia. Brain 127:1061-1074.
41. Hensley K, Carney JM, Mattson MP, Aksenova M, Harris M, Wu JF, Floyd RA, Butterfield DA (1994) A model for β-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci USA 91:3270-3274.
42. Herzig MC, Winkler DT, Burgermeister P, Pfeifer M, Kohler E, Schmidt SD, Danner S, Abramowski D, Sturchler-Pierrat C, Burki K, Van Duinen SG, Maat-Schieman ML, Staufenbiel M, Mathews PM, Jucker M (2004) Aβ is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis. Nat Neurosci 7:954-960.
43. Higgins GA, Jacobsen H (2003) Transgenic mouse models of Alzheimer's disease: phenotype and application. Behav Pharmacol 14:419-438.
44. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer's disease. J Neurosci 21:3017-3023.
45. Hovatta I, Tennant RS, Helton R, Marr RA, Singer O, Redwine JM, Ellison JA, Schadt EE, Verma IM, Lockhart DJ, Barlow C (2005) Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice. Nature 438:662-666.
46. Hsia A, Masliah E, McConlogue L, Yu G, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L (1999) Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci USA 96:3228-3233.
47. Huang TT, Carlson EJ, Kozy HM, Mantha S, Goodman SI, Ursell PC, Epstein CJ (2001) Genetic modification of prenatal lethality and dilated cardiomyopathy in Mn superoxide dismutase mutant mice. Free Radic Biol Med 31:1101-1110.
48. Iadecola C, Zhang F, Niwa K, Eckman C, Turner SK, Fischer E, Younkin S, Borchelt DR, Hsiao KK, Carlson GA (1999) SOD 1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat Neurosci 2:157-161.
49. 42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci USA 94:1550-1555.
50. Kabe Y, Ando K, Hirao S, Yoshida M, Handa H (2005) Redox regulation of NF-κB activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid Redox Signal 7:395-403.
51. Kanazawa H, Ohsawa K, Sasaki Y, Kohsaka S, Imai Y (2002) Macrophage/microglia-specific protein Iba1 enhances membrane ruffling and Rac activation via phospholipase C-γ-dependent pathway. J Biol Chem 277:20026-20032.
52. Keil U, Bonert A, Marques CA, Scherping I, Weyermann J, Strosznajder JB, Muller-Spahn F, Haass C, Czech C, Pradier L, Muller WE, Eckert A (2004) Amyloid β-induced changes in nitric oxide production and mitochondrial activity lead to apoptosis. J Biol Chem 279:50310-50320.
53. Kim GW, Kondo T, Noshita N, Chan PH (2002) Manganese superoxide dismutase deficiency exacerbates cerebral infarction after focal cerebral ischemia/reperfusion in mice: implications for the production and role of superoxide radicals. Stroke 33:809-815.
54. Knowles RB, Wyart C, Buldyrev SV, Cruz L, Urbanc B, Hasselmo ME, Stanley HE, Hyman BT (1999) Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer's disease. Proc Natl Acad Sci USA 96:5274-5279.
55. Kobayashi DT, Chen KS (2005) Behavioral phenotypes of amyloid-based genetically modified mouse models of Alzheimer's disease. Genes Brain Behav 4:173-196.
56. Kokoszka JE, Coskun P, Esposito LA, Wallace DC (2001) Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis. Proc Natl Acad Sci USA 98:2278-2283.
57. Krömer SA, Kessler MS, Milfay D, Birg IN, Bunck M, Czibere L, Panhuysen M, Pütz B, Deussing JM, Holsboer F, Landgraf R, Turck CW (2005) Identification of glyoxalase-I as a protein marker in a mouse model of extremes in trait anxiety. J Neurosci 25:4375-4384.
58. Kuo YM, Beach TG, Sue LI, Scott S, Layne KJ, Kokjohn TA, Kalback WM, Luehrs DC, Vishnivetskaya TA, Abramowski D, Sturchler-Pierrat C, Staufenbiel M, Weller RO, Roher AE (2001) The evolution of A beta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease. Mol Med 7:609-618.
59. Lebovitz RM, Zhang HJ, Vogel H, Cartwright JJ, Dionne L, Lu NF, Huang S, Matzuk MM (1996) Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci USA 93:9782-9787.
60. Li F, Calingasan NY, Yu F, Mauck WM, Toidze M, Almeida CG, Takahashi RH, Carlson GA, Flint Beal M, Lin MT, Gouras GK (2004) Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J Neurochem 89:1308-1312.
61. Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (1995) Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11:376-381.
62. -/+ mice. Free Radic Biol Med 36:542-554.
63. Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, McDowell I (2002) Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 156:445-453.
64. Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180-185.
65. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, et al. (2004) ABAD directly links Aβ to mitochondrial toxicity in Alzheimer's disease. Science 304:448-452.
66. Masliah E, Mallory M, Hansen L, Alford M, DeTeresa R, Terry R (1993) An antibody against phosphorylated neurofilaments identifies a subset of damaged association axons in Alzheimer's disease. Am J Pathol 142:871-882.
67. Masliah E, Alford M, Mallory M, Rockenstein E, Moechars D, Van Leuven F (2000) Abnormal glutamate transport function in mutant amyloid precursor protein transgenic mice. Exp Neurol 163:381-387.
68. May MJ, Ghosh S (1998) Signal transduction through NF-κB. Immunol Today 19:80-88.
69. Mazur-Kolecka B, Dickson D, Frackowiak J (2006) Induction of vascular amyloidosis-β by oxidative stress depends on APOE genotype. Neurobiol Aging, in press.
70. McCool MF, Varty GB, Del Vecchio RA, Kazdoba TM, Parker EM, Hunter JC, Hyde LA (2003) Increased auditory startle response and reduced prepulse inhibition of startle in transgenic mice expressing a double mutant form of amyloid precursor protein. Brain Res 994:99-106.
71. Melov S, Schneider JA, Day BJ, Hinerfeld D, Coskun P, Mirra SS, Crapo JD, Wallace DC (1998) A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase. Nat Genet 18:159-163.
72. 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20:4050-4058.
73. Munoz DG, Feldman H (2000) Causes of Alzheimer's disease. CMAJ 162:65-72.
74. Mutisya EM, Bowling AC, Beal MF (1994) Cortical cytochrome oxidase activity is reduced in Alzheimer's disease. J Neurochem 63:2179-2184.
75. Nadeau S, Rivest S (2000) Role of microglial-derived tumor necrosis factor in mediating CD14 transcription and nuclear factor κB activity in the brain during endotoxemia. J Neurosci 20:3456-3468.
76. Omar RA, Chyan YJ, Andorn AC, Poeggeler B, Robakis NK, Pappolla MA (1999) Increased expression but reduced activity of antioxidant enzymes in Alzheimer's disease. J Alzheimers Dis 1:139-145.
77. Onorato M, Mulvihill P, Connolly J, Galloway P, Whitehouse P, Perry G (1989) Alteration of neuritic cytoarchitecture in Alzheimer disease. Prog Clin Biol Res 317:781-789.
78. Palop JJ, Jones B, Kekonius L, Chin J, Yu G-Q, Raber J, Masliah E, Mucke L (2003) Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc Natl Acad Sci USA 100:9572-9577.
79. Palop JJ, Chin J, Bien-Ly N, Massaro C, Yeung BZ, Yu G-Q, Mucke L (2005) Vulnerability of dentate granule cells to disruption of Arc expression in human amyloid precursor protein transgenic mice. J Neurosci 25:9686-9693.
80. Pellow S, Chopin R, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149-167.
81. Praticò D (2002) Alzheimer's disease and oxygen radicals: new insights. Biochem Pharmacol 63:563-567.
82. -/- mice: Possible role in behavioral and metabolic alterations. J Neurosci 20:2064-2071.
83. Raber J, Wong D, Yu G-Q, Buttini M, Mahley RW, Pitas RE, Mucke L (2000b) Alzheimer's disease: apolipoprotein E and cognitive performance. Nature 404:352-354.
84. Raber J, LeFevour A, Buttini M, Mucke L (2002) Androgens protect against apolipoprotein E4-induced cognitive deficits. J Neurosci 22:5204-5209.
85. 1-42. J Neurosci Res 66:573-582.
86. Rockenstein E, Mante M, Alford M, Adame A, Crews L, Hashimoto M, Esposito L, Mucke L, Masliah E (2005) High β-Secretase activity elicits neurodegeneration in transgenic mice despite reductions in amyloid-β levels: Implications for the treatment of Alzheimer's disease. J Biol Chem 280:32957-32967.
87. (SWE). Neurobiol Dis 12:194-211.
88. Selkoe DJ, Schenk D (2003) Alzheimer's disease: Molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43:545-584.
89. Simard AR, Soulet D, Gowing G, Julien JP, Rivest S (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 49:489-502.
90. Staal FJ, Roederer M, Herzenberg LA (1990) Intracellular thiols regulate activation of nuclear factor κB and transcription of human immunodeficiency virus. Proc Natl Acad Sci USA 87:9943-9947.
91. Sun SC, Elwood J, Beraud C, Greene WC (1994) Human T-cell leukemia virus type I Tax activation of NF-κB/Rel involves phosphorylation and degradation of IκBα and RelA (p65)-mediated induction of the c-rel gene. Mol Cell Biol 14:7377-7384.
92. Takeuchi H, Mizuno T, Zhang G, Wang J, Kawanokuchi J, Kuro R, Suzumura A (2005) Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport. J Biol Chem 280:10444-10454.
93. Tanzi R, Bertram L (2005) Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 120:545-555.
94. Tong XK, Nicolakakis N, Kocharyan A, Hamel E (2005) Vascular remodeling versus amyloid β-induced oxidative stress in the cerebrovascular dysfunctions associated with Alzheimer's disease. J Neurosci 25:11165-11174.
95. Van Dorpe J, Smeijers L, Dewachter I, Nuyens D, Spittaels K, Van den Haute C, Mercken M, Moechars D, Laenen I, Kuiperi C, Bruynseels K, Tesseur I, Loos R, Vanderstichele H, Checler F, Sciot R, Van Leuven F (2000) Prominent cerebral amyloid angiopathy in transgenic mice overexpressing the London mutant of human APP in neurons. Am J Pathol 157:1283-1298.
96. Van Remmen H, Williams MD, Guo Z, Estlack L, Yang H, Carlson EJ, Epstein CJ, Huang TT, Richardson A (2001) Knockout mice heterozygous for Sod2 show alterations in cardiac mitochondrial function and apoptosis. Am J Physiol Heart Circ Physiol 281:H1422-H1432.
97. Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR, Alderson NL, Baynes JW, Epstein CJ, Huang TT, Nelson J, Strong R, Richardson A (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16:29-37.
98. Van Uden E, Mallory M, Veinbergs I, Alford M, Rockenstein E, Masliah E (2002) Increased extracellular amyloid deposition and neurodegeneration in human amyloid precursor protein transgenic mice deficient in receptor-associated protein. J Neurosci 22:9298-9304.
99. Veki A, Goto K, Sato N, Iso H, Morita Y (2006) Prepulse inhibition of acoustic startle response in mild cognitive impairment and mild dementia of Alzheimer type. Psychiatry Clin Neurosci 60:55-62.
100. Walton JP, Frisina RD, Meierhans LR (1995) Sensorineural hearing loss alters recovery from short-term adaptation in the C57BL/6 mouse. Hear Res 88:19-26.
101. Wang Q, Rowan MJ, Anwyl R (2004) β-amyloid-mediated inhibition of NMDA receptor-dependent long-term potentiation induction involves activation of microglia and stimulation of inducible nitric oxide synthase and superoxide. J Neurosci 24:6049-6056.
102. Williams MD, Van Remmen H, Conrad CC, Huang TT, Epstein CJ, Richardson A (1998) Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice. J Biol Chem 273:28510-28515.
103. Wyss-Coray T, Mucke L (2002) Inflammation in neurodegenerative disease-a double-edged sword. Neuron 35:419-432.
104. Wyss-Coray T, Masliah E, Mallory M, McConlogue L, Johnson-Wood K, Lin C, Mucke L (1997) Amyloidogenic role of cytokine TGF-β1 in transgenic mice and Alzheimer's disease. Nature 389:603-606.
105. Wyss-Coray T, Lin C, Von Euw D, Masliah E, Mucke L, Lacombe P (1999) Alzheimer's disease-like cerebrovascular pathology in transforming growth factor-β1 transgenic mice and functional metabolic correlates. Ann NY Acad Sci 903:317-323.
106. Wyss-Coray T, Lin C, Sanan D, Mucke L, Masliah E (2000) Chronic overproduction of TGF-β1 in astrocytes promotes Alzheimer's disease-like microvascular degeneration in transgenic mice. Am J Pathol 156:139-150.
107. Wyss-Coray T, Lin C, Yan F, Yu G-Q, Rohde M, McConlogue L, Masliah E, Mucke L (2001) TGF-β1 promotes microglial amyloid-β clearance and reduces plaque burden in transgenic mice. Nat Med 7:612-618.