期刊
IBRO NEUROSCIENCE REPORTS
卷 12, 期 -, 页码 131-141出版社
ELSEVIER
DOI: 10.1016/j.ibneur.2022.01.004
关键词
Alzheimer's disease; Dementia; Knock-in; App( NL-G-F/NL-G-F) ; Lysosome; beta-hexosaminidase; Hexb
资金
- Australian Rotary Health/Rotary Club of Adelaide Funding Partner Scholarship
- Lysosomal Health in Ageing, Lifelong Health Theme, SAHMRI
Lysosomal network abnormalities are a significant feature of Alzheimer's disease, and reduced expression of the Hexb gene may lead to related pathological changes and behavioral alterations in an AD model mouse.
Lysosomal network abnormalities are an increasingly recognised feature of Alzheimer's disease (AD), which appear early and are progressive in nature. Sandhoff disease and Tay-Sachs disease (neurological lysosomal storage diseases caused by mutations in genes that code for critical subunits of beta-hexosaminidase) result in accumulation of amyloid-beta (A beta) and related proteolytic fragments in the brain. However, experiments that determine whether mutations in genes that code for beta-hexosaminidase are risk factors for AD are currently lacking. To determine the relationship between beta-hexosaminidase and AD, we investigated whether a heterozygous deletion of Hexb, the gene that encodes the beta subunit of beta-hexosaminidase, modifies the behavioural phenotype and appearance of disease lesions in App(NL-G-F/NL-G-F) (App(KI/KI)) mice. App(KI/KI) and Hexb(+/-& nbsp;)mice were crossed and evaluated in a behavioural test battery. Neuropathological hallmarks of AD and ganglioside levels in the brain were also examined. Heterozygosity of Hexb in App(KI/KI) mice reduced learning flexibility during the Reversal Phase of the Morris water maze. Contrary to expectation, heterozygosity of Hexb caused a small but significant decrease in amyloid beta deposition and an increase in the microglial marker IBA1 that was region and age-specific. Hexb heterozygosity caused detectable changes in the brain and in the behaviour of an AD model mouse, consistent with previous reports that described a biochemical relationship between HEXB and AD. This study reveals that the lysosomal enzyme gene Hexb is not haplosufficient in the mouse AD brain.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据