title: Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats.
abstract: The amyloid cascade hypothesis posits that deposition of the amyloid β (Aβ) peptide in the brain is a key event in the initiation of Alzheimer's disease (AD). Nonetheless, it now seems increasingly unlikely that amyloid toxicity is the cause of sporadic AD, which leads to cognitive decline. Here, using accelerated-senescence nontransgenic OXYS rats, we confirmed that aggregation of Aβ is a later event in AD-like pathology. We showed that an age-dependent increase in the levels of Aβ₁₋₄₂ and extracellular Aβ deposits in the brain of OXYS rats occur later than do synaptic losses, neuronal cell death, mitochondrial structural abnormalities, and hyperphosphorylation of the tau protein. We identified the variants of the genes that are strongly associated with the risk of either late-onset or early-onset AD, including App, Apoe4, Bace1, Psen1, Psen2, and Picalm. We found that in OXYS rats nonsynonymous SNPs were located only in the genes Casp3 and Sorl1. Thus, we present proof that OXYS rats may be a model of sporadic AD. It is possible that multiple age-associated pathological processes may precede the toxic amyloid accumulation, which in turn triggers the final stage of the sporadic form of AD and becomes a hallmark event of the disease.
authors.affiliation: Institute of Cytology and Genetics, Novosibirsk, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Stefanova
authors.affiliation: Institute of Cytology and Genetics, Novosibirsk, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Muraleva
authors.affiliation: Institute of Cytology and Genetics, Novosibirsk, Russia.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Korbolina
authors.affiliation: Institute of Cytology and Genetics, Novosibirsk, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Kiseleva
authors.affiliation: Siberian State Medical University, Tomsk, Russia.
authors.forename: Kseniya Yi
authors.initials: KY
authors.lastname: Maksimova
authors.affiliation: Institute of Cytology and Genetics, Novosibirsk, Russia.|Institute of Mitoengineering, Moscow, Russia.|Novosibirsk State University, Novosibirsk, Russia.
authors.forename: Nataliya G
authors.initials: NG
authors.lastname: Kolosova
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides