Amyloid precursor protein and presenilin-1 knock-in immunodeficient mice exhibit intraneuronal Aβ pathology, microgliosis, and extensive neuronal loss.

ABSTRACT:

Introduction

Transgenic mice overexpressing familial Alzheimer's disease (AD) mutations (FAD) show non-physiological traits, and their immunocompetent backgrounds limit their use in AD immunotherapy research. Preclinical models that reflect human immune responses in AD are needed.

Methods

Using CRISPR-Cas9, we developed single (NA) and double (NAPS) knock-in (KI) amyloid precursor protein (APP)^KM670,671NL (Swedish) and presenilin 1 (PS 1)^M146VFAD mutations on an immunodeficient NOG (NOD.Cg-Prkdc^scidIl2rg^tm1Sug/JicTac) background. The models were confirmed by Sanger sequencing and evaluated for AD-like pathology.

Results

Both NA and NAPS mice developed pathology without overexpression artifacts. Mutation-induced upregulation

SUBMITTER: Yeapuri P 

PROVIDER: S-EPMC11975631 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature