Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE ɛ2 for Alzheimer's disease.

ABSTRACT:

Introduction

The apolipoprotein E (APOE) ɛ2 allele reduces risk against Alzheimer's disease (AD) but mechanisms underlying this effect are largely unknown.

Methods

We conducted a genome-wide association study for AD among 2096 ɛ2 carriers. The potential role of the top-ranked gene and complement 4 (C4) proteins, which were previously linked to AD in ɛ2 carriers, was investigated using human isogenic APOE allele-specific induced pluripotent stem cell (iPSC)-derived neurons and astrocytes and in 224 neuropathologically examined human brains.

Results

PPP2CB rs117296832 was the second most significantly associated single nucleotide polymorphism among ɛ2 carriers (P = 1.1 × 10^-7 ) and the AD risk allele increased PPP2CB expression in blood (P = 6.6 × 10^-27<

SUBMITTER: Jun GR 

PROVIDER: S-EPMC9360190 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature