Title:Decreased Myelinated Fibers in the Hippocampal Dentate Gyrus of the Tg2576 Mouse Model of Alzheimer’s Disease
VOLUME: 13 ISSUE: 9
Author(s):Wei Lu, Shu Yang, Lei Zhang, Lin Chen, Feng-Lei Chao, Yan-min Luo, Qian Xiao, Heng-Wei Gu, Rong Jiang and Yong Tang
Affiliation:Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, P.R. China.
Keywords:Alzheimer’s disease, Aβ, hippocampus, myelinated fiber, stereology, Tg2576 mouse.
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.
