CRISPR manipulated human fibroblasts as a model for Alzheimer's disease
November 2017
Columbia University Medical Center, New York, USA
Alzheimer's disease main causative hypothesis in the last years is the amyloid hypothesis: several alterations in the processing of amyloid precursor protein lead to an accumulation of amyloid-beta that results in brain degeneration. Some of these alterations in the familial version are related to gene mutations considered as risk factors. Two of them are mutations in the presenilin 1 and 2 genes, components of the gamma-secretase complex that produces amyloid-beta. In this study, an in vitro model based on human skin fibroblasts from familial Alzheimer's disease patients is used to study the effect of the activation of endogenous genes related to the disease. Through CRISPR manipulation, the researchers describe that the activation of amyloid precursor protein and/or beta-secretase genes shows a defective cleavage of gamma-secretase that leads to amyloid-beta 42 accumulation. Here, an easy-to-obtain and -use model described that can help to uncover pathogenic mechanisms through controlled manipulation of specific genes directly in patient samples.
CRISPR transcriptional activation analysis unmasks an occult g-secretase processivity defect in familial Alzheimer’s disease skin fibroblasts
Asa Abeliovich, Keiichi Inoue
Added on: 08-20-2021
[1] https://www.cell.com/cell-reports/fulltext/S2211-1247(17)31538-3[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
