TOMM40 and APOE Gene Expression and Cognitive Decline in Japanese Alzheimer's Disease Subjects.
J Alzheimers Dis
; 60(3): 1107-1117, 2017.
Article
in En
| MEDLINE
| ID: mdl-28984592
ABSTRACT
BACKGROUND:
TOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), andis reported in several genome-wide association studies to be associated with Alzheimer's disease (AD).OBJECTIVE:
Assess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD.METHODS:
We examined TOMM40, PTEN-induced putative kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PARK2), and APOE mRNA expression in relation to the methylation rates of CpG sites in the upstream region of TOMM40exon 1 in peripheral leukocytes and TOMM40523 polyT genotypes in 60 AD and age- and sex-matched control subjects.RESULTS:
TOMM40 mRNA expression was significantly lower in AD subjects (0.87±0.18 versus 1.0±0.23, pâ=â0.005), and PINK1 mRNA expression was higher in AD subjects (1.5±0.61 versus 1.0±0.52, pâ<â0.001). TOMM40 mRNA expression was significantly correlated with the Mini-Mental State Examination total score (râ=â0.290, pâ=â0.027). There was no expressional change in peripheral APOE mRNA in either AD or control subjects (pâ=â0.32). Methylation rates in the upstream region of TOMM40exon 1 were not different between AD and control subjects (average rate 1.37±0.99 versus 1.39±1.20, pâ=â0.885), and TOMM40523 polyT genotypes were also not different between AD and control subjects (pâ=â0.67).CONCLUSION:
TOMM40 mRNA expression was lower in AD subjects and was correlated with cognitive decline. Significant changes in both TOMM40 and PINK1 mRNA may be related to mitochondrial dysfunction.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apolipoproteins E
/
Membrane Transport Proteins
/
Alzheimer Disease
/
Cognitive Dysfunction
Limits:
Aged
/
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
J Alzheimers Dis
Journal subject:
GERIATRIA
/
NEUROLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Japan