Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE É2 for Alzheimer's disease.
Alzheimers Dement
; 18(11): 2042-2054, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35142023
ABSTRACT
INTRODUCTION:
The apolipoprotein E (APOE) É2 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 É2 carriers. The potential role of the top-ranked gene and complement 4 (C4) proteins, which were previously linked to AD in É2 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 É2 carriers (P = 1.1 × 10-7 ) and the AD risk allele increased PPP2CB expression in blood (P = 6.6 × 10-27 ). PPP2CB expression was correlated with phosphorylated tau231/total tau ratio (P = .01) and expression of C4 protein subunits C4A/B (P = 2.0 × 10-4 ) in the iPSCs. PPP2CB (subunit of protein phosphatase 2A) and C4b protein levels were correlated in brain (P = 3.3 × 10-7 ).DISCUSSION:
PP2A may be linked to classical complement activation leading to AD-related tau pathology.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article