EPIGENOMIC FEATURES RELATED TO MICROGLIA ARE ASSOCIATED WITH ATTENUATED EFFECT OF APOE ε4 ON ALZHEIMER'S DISEASE RISK IN HUMANS.
Alzheimers Dement
; 16(Suppl 2)2020 12.
Article
en En
| MEDLINE
| ID: mdl-34393677
ABSTRACT
Not all APOE ε4 carriers who survive to advanced age develop Alzheimer's disease (AD); factors attenuating the risk of ε4 on AD may exist. Guided by the top ε4-attenuating signals from methylome-wide association analyses (N=572, ε4+ and ε4-) of neurofibrillary tangles and neuritic plaques, we conducted a meta-analysis for pathological AD within the ε4+ subgroups (N=235) across four independent collections of brains. Cortical RNA-seq and microglial morphology measurements were used in functional analyses. Three out of the four significant CpG dinucleotides were captured by one principle component (PC1), which interacts with ε4 on AD, and is associated with expression of innate immune genes and activated microglia. In ε4 carriers, reduction in each unit of PC1 attenuated the odds of AD by 58% (OR=2.39, 95%CI=[1.64,3.46], P=7.08x10-6). An epigenomic factor associated with a reduced proportion of activated microglia (microglial epigenomic factor 1) appears to attenuate the risk of ε4 on AD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Microglía
/
Apolipoproteína E4
/
Epigenómica
/
Enfermedad de Alzheimer
/
Heterocigoto
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Alzheimers Dement
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos