Early molecular events of autosomal-dominant Alzheimer's disease in marmosets with PSEN1 mutations.

ABSTRACT:

Introduction

Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically engineered marmosets that carry knock-in (KI) point mutations in the presenilin 1 (PSEN1) gene that can be studied from birth throughout lifespan.

Methods

CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1. Founders and their germline offspring are comprehensively studied longitudinally using non-invasive measures including behavior, biomarkers, neuroimaging, and multiomics signatures.

Results

Prior to adulthood, increases in plasma amyloid beta were observed in PSEN1 mutation carriers relative to non-carriers. Analys

SUBMITTER: Homanics GE 

PROVIDER: S-EPMC11095452 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature