title: Brain Amyloid-β Plays an Initiating Role in the Pathophysiological Process of the PS1V97L-Tg Mouse Model of Alzheimer's Disease.
abstract: Amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, and neuroinflammation are major pathophysiological events in Alzheimer's disease (AD). However, the relationships among these processes and which first exerts an effect are unknown. In the present study, we investigated age-dependent behavioral changes and the sequential pathological progression from the brain to the periphery in AD transgenic (PS1V97L-Tg) mice and their wild-type littermates. We discovered that the brain Aβ significantly increased at 6 months old, the increased brain Aβ caused memory dysfunction, and the ability of Aβ to induce tau hyperphosphorylation might be due to oxidative stress and neuroinflammatory reactions. The levels of Aβ42, total tau (t-tau), oxidative stress parameters, and proinflammatory cytokines in plasma can be used to differentiate between PS1V97L-Tg mice and their wild-type littermates at different time points. Collectively, our findings support the hypothesis that Aβ is a trigger among these pathophysiological processions and show that plasma biomarkers can reflect the condition of the AD brain.
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.|Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, P.R. China.|Beijing Key Laboratory for Geriatric Cognitive Disorders, Beijing, P.R. China.|Key Neurodegenerative Laboratory of the Ministry of Education of the People's Republic of China, Beijing, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.|Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, P.R. China.|Beijing Key Laboratory for Geriatric Cognitive Disorders, Beijing, P.R. China.|Key Neurodegenerative Laboratory of the Ministry of Education of the People's Republic of China, Beijing, P.R. China.
authors.forename: Qiao-Qi
authors.initials: QQ
authors.lastname: Wu
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.|Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, P.R. China.|Beijing Key Laboratory for Geriatric Cognitive Disorders, Beijing, P.R. China.|Key Neurodegenerative Laboratory of the Ministry of Education of the People's Republic of China, Beijing, P.R. China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Jia
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016207:Cytokines; D016875:tau Proteins
keywords: Alzheimer’s disease; PS1V97L-Tg mouse; amyloid-β; oxidative stress; proinflammatory cytokines; tau