TY - JOUR
T1 - Neurodegeneration in Amygdala precedes hippocampus in the APPswe/PS1dE9 mouse model of Alzheimer’s disease
AU - Lin, Tzu Wei
AU - Liu, Yu Fan
AU - Shih, Yao Hsiang
AU - Chen, Shean Jen
AU - Huang, Tung Yi
AU - Chang, Chia-Yuan
AU - Lien, Chi Hsiang
AU - Yu, Lung
AU - Chen, Shun-hua
AU - Kuo, Yu-Min
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84959575021&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959575021&partnerID=8YFLogxK
U2 - 10.2174/1567205012666151027124938
DO - 10.2174/1567205012666151027124938
M3 - Article
C2 - 26502818
AN - SCOPUS:84959575021
SN - 1567-2050
VL - 12
SP - 951
EP - 963
JO - Current Alzheimer research
JF - Current Alzheimer research
IS - 10
ER -