Decoding the Role of an Alzheimer's Causal Gene in Distinct Brain Cell Types

Project Summary

Mutations in the gene encoding presenilin2 (PSEN2) cause early onset familial Alzheimer’s disease but thus far this was mainly studied in the context of a build-up of toxic amyloid aggregates. However given its restricted localization in degradative compartments, we hypothesize that mechanisms exist leading to disease onset that may differ from its close relative PSEN1. Utilizing new PSEN2 AD mouse models and human neurons/microglia, we will employ functional assays and advanced morphological studies to unravel the cell type specific contributions of PSEN2 in AD etiopathogenesis.