APOE ε4-dependent effects on the early amyloid pathology in induced neurons of patients with Alzheimer's disease.

ABSTRACT:

Background

The ε4 allele of apolipoprotein E (APOE ε4) is the strongest known genetic risk factor for late-onset Alzheimer's disease (AD), associated with amyloid pathogenesis. However, it is not clear how APOE ε4 accelerates amyloid-beta (Aβ) deposition during the seeding stage of amyloid development in AD patient neurons.

Methods

AD patient induced neurons (iNs) with an APOE ε4 inducible system were prepared from skin fibroblasts of AD patients. Transcriptome analysis was performed using RNA isolated from the AD patient iNs expressing APOE ε4 at amyloid-seeding and amyloid-aggregation stages. Knockdown of IGFBP3 was applied in the iNs to investigate the role of IGFBP3 in the APOE ε4-mediated amyloidosis.

Results

We optimized amyloid seeding stage in the iNs of AD pa

SUBMITTER: Kim H 

PROVIDER: S-EPMC9594913 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature