Neurodegeneration in Amygdala precedes hippocampus in the APPswe/PS1dE9 mouse model of Alzheimer’s disease

Tzu Wei Lin, Yu Fan Liu, Yao Hsiang Shih, Shean Jen Chen, Tung Yi Huang, Chia-Yuan Chang, Chi Hsiang Lien, Lung Yu, Shun-hua Chen, Yu-Min Kuo

研究成果: Article同行評審

10 引文 斯高帕斯(Scopus)

摘要

Both the hippocampus and amygdala are early vulnerable brain regions in the development of Alzheimer’s disease (AD). However, previous studies mainly focused on characterizing the hippocampus in the pathophysiology of AD, leaving the amygdala less explored. Here, we characterized the structures and functions of neurons in the hippocampus and amygdala of young (2, 3 and 4 months of age) APP/PS1 double transgenic (Tg) mice, a widely used AD mouse model. Compared to wild-type littermates (Wt), Tg mice performed worse in amygdala-dominant memory at all three ages, while hippocampus-dominant memory remained intact until 4-month-old. Likewise, the dendritic arbors of neurons in the basolateral amygdala were reduced in Tg mice as early as 2-months-old, while the dendritic arbors of neurons in the hippocampal CA1 and CA3 regions were relatively intact. BDNF signaling pathways (e.g. AKT and PKC) were reduced in the amygdala, but not in the hippocampus, of young Tg mice. Furthermore, reduction of 5-HT and elevation of Aβ levels also occurred earlier in the amygdala and were more pronounced than those in the hippocampus. Negative correlations between the levels of 5-HT and Aβ were evident in the amygdala, but not in the hippocampus. Taken together, these results suggest that neurodegeneration occurs earlier in the amygdala than in the hippocampus. We suggest that amygdala function should be incorporated into the cognitive screening tool for the diagnosis of mild cognitive impairment due to AD.

原文English
頁(從 - 到)951-963
頁數13
期刊Current Alzheimer research
12
發行號10
DOIs
出版狀態Published - 2015 十二月 1

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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