Early blood immune molecular alterations in cynomolgus monkeys with a PSEN1 mutation causing familial Alzheimer's disease.

ABSTRACT:

Introduction

More robust non-human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD.

Methods

We designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3' and 5' intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome, and biomarker analyses to characterize the cellular and molecular dysregulations of this non-human primate model.

Results

We observed early changes of AD-related pathological proteins (cerebrospinal fluid Aβ₄₂ and phosphorylated tau) in PSEN1 mutant (ie, PSEN1-ΔE9) monkeys. Blood transcriptome and proteome profiling revealed early changes in inflammatory a

SUBMITTER: Li M 

PROVIDER: S-EPMC11350033 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature