Elucidating a microgliaassociated role for SORLA in modulating AD pathogenesis
Description: PROJECT NARRATIVE In this study, we isogenically integrated Alzheimer’s disease (AD)-associated mutations in genes such as SORLA in human embryonic stem cells (H9), and subsequently differentiated recombinant cell lines into human microglia-like cells (hMGLs). Our results indicate that AD-associated mutations in SORLA such as A528T and R744X can impact various aspects of microglia function in vitro (such as Aβ uptake), and in vivo (Aβ clearance). This study will compare and characterize effects of other SORLA mutations identified in early and onset AD using a mouse brain/human microglia xenotransplant model, and determine potential pathogenic mechanisms for SORLA-dependent microglial dysfunction in AD.
Funder: National Institute on Aging
Funding type: research
Funder scheme: RF1
Start date: 2022-08-01
End date: 2025-07-31
Investigator: TIMOTHY YIKAI HUANG
Institution: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Funded outputs count: 3
Funder award ID: RF1AG070391
OpenAlex ID: G3324084579