当前位置: X-MOL 学术Mol. Neurodegener. › 论文详情
Contribution of GABAergic interneurons to amyloid-β plaque pathology in an APP knock-in mouse model.
Molecular Neurodegeneration ( IF 8.274 ) Pub Date : 2020-01-08 , DOI: 10.1186/s13024-019-0356-y
Heather C Rice,Gabriele Marcassa,Iordana Chrysidou,Katrien Horré,Tracy L Young-Pearse,Ulrike C Müller,Takashi Saito,Takaomi C Saido,Robert Vassar,Joris de Wit,Bart De Strooper

The amyloid-β (Aβ) peptide, the primary constituent of amyloid plaques found in Alzheimer's disease (AD) brains, is derived from sequential proteolytic processing of the Amyloid Precursor Protein (APP). However, the contribution of different cell types to Aβ deposition has not yet been examined in an in vivo, non-overexpression system. Here, we show that endogenous APP is highly expressed in a heterogeneous subset of GABAergic interneurons throughout various laminae of the hippocampus, suggesting that these cells may have a profound contribution to AD plaque pathology. We then characterized the laminar distribution of amyloid burden in the hippocampus of an APP knock-in mouse model of AD. To examine the contribution of GABAergic interneurons to plaque pathology, we blocked Aβ production specifically in these cells using a cell type-specific knock-out of BACE1. We found that during early stages of plaque deposition, interneurons contribute to approximately 30% of the total plaque load in the hippocampus. The greatest contribution to plaque load (75%) occurs in the stratum pyramidale of CA1, where plaques in human AD cases are most prevalent and where pyramidal cell bodies and synaptic boutons from perisomatic-targeting interneurons are located. These findings reveal a crucial role of GABAergic interneurons in the pathology of AD. Our study also highlights the necessity of using APP knock-in models to correctly evaluate the cellular contribution to amyloid burden since APP overexpressing transgenic models drive expression in cell types according to the promoter and integration site and not according to physiologically relevant expression mechanisms.
更新日期:2020-04-22

 

全部期刊列表>>
聚焦商业经济政治法律
跟Nature、Science文章学绘图
智控未来
控制与机器人
化学研究精选
欢迎探索2019年最具下载量的地球科学论文
招募海内外科研人才,上自然官网
基因组学对精准公共卫生的影响,专辑征稿
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
x-mol收录
湖南大学化学化工学院刘松
上海有机所
李旸
大连化物所
香港大学
X-MOL
支志明
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug