Neurodegeneration in Amygdala Precedes Hippocampus in the APPswe/ PS1dE9 Mouse Model of Alzheimer's Disease.
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.
Tzu-Wei
TW
Lin
Yu-Fan
YF
Liu
Yao-Hsiang
YH
Shih
Shean-Jen
SJ
Chen
Tung-Yi
TY
Huang
Chia-Yuan
CY
Chang
Chi-Hsiang
CH
Lien
Lung
L
Yu
Shun-Hua
SH
Chen
Department of Cell Biology and Anatomy, National Cheng Kung, University. 1 Ta Hsueh Road, Tainan, Taiwan 70101. kuoym@mail.ncku.edu.tw.
Yu-Min
YM
Kuo
D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D000679:Amygdala / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003213:Conditioning, Psychological / Q000502:physiology; D003712:Dendrites / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology; D012701:Serotonin / Q000378:metabolism
C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D012701:Serotonin; D006897:Hydroxyindoleacetic Acid