title: Decreased Myelinated Fibers in the Hippocampal Dentate Gyrus of the Tg2576 Mouse Model of Alzheimer's Disease.
abstract: Alzheimer's disease (AD), the most common cause of dementia in the elderly, is characterized by deficits in cognition and memory. Although amyloid-β (Aβ) accumulation is known to be the earliest pathological event that triggers subsequent neurodegeneration, how Aβ accumulation causes behavioral deficits remains incompletely understood. In this study, using the Morris water maze test, ELISA and stereological methods, we examined spatial learning and memory performance, the soluble Aβ concentration and the myelination of fibers in the hippocampus of 4-, 6-, 8- and 10-month-old Tg2576 AD model mice. Our results showed that spatial learning and memory performance was significantly impaired in the Tg2576 mice compared to the wild type (WT) controls and that the myelinated fiber length in the hippocampal dentate gyrus (DG) was markedly decreased from 0.33 ± 0.03 km in the WT controls to 0.17 ± 0.02 km in the Tg2576 mice at 10 months of age. However, the concentrations of soluble Aβ40 and Aβ42 were significantly increased as early as 4-6 months of age. The decreased myelinated fiber length in the DG may contribute to the spatial learning and memory deficits of Tg2576 mice. Therefore, we suggest that the significant accumulation of soluble Aβ may serve as a preclinical biomarker for AD diagnosis and that protecting myelinated fibers may represent a novel strategy for delaying the progression of early-stage AD.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Feng-Lei
authors.initials: FL
authors.lastname: Chao
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Luo
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiao
authors.forename: Heng-Wei
authors.initials: HW
authors.lastname: Gu
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, P.R. China. ytang062@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D018782:Maze Learning; D008568:Memory; D008822:Mice, Transgenic; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size; D010446:Peptide Fragments / Q000378:metabolism; D011897:Random Allocation
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)