TOMM40 and APOE Gene Expression and Cognitive Decline in Japanese Alzheimer's Disease Subjects

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). Assess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD. We examined TOMM40,...

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Veröffentlicht in:Journal of Alzheimer's disease Jg. 60; H. 3; S. 1107
Hauptverfasser: Mise, Ayano, Yoshino, Yuta, Yamazaki, Kiyohiro, Ozaki, Yuki, Sao, Tomoko, Yoshida, Taku, Mori, Takaaki, Mori, Yoko, Ochi, Shinichiro, Iga, Jun-Ichi, Ueno, Shu-Ichi
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands 01.01.2017
Schlagworte:
Aged
Alzheimer Disease - blood
Alzheimer Disease - genetics
Apolipoproteins E - blood
Biomarkers - blood
Cognitive Dysfunction - blood
Cognitive Dysfunction - genetics
CpG Islands
DNA Methylation
Female
Gene Expression
Humans
Japan
Male
Membrane Transport Proteins - blood
Membrane Transport Proteins - genetics
Mental Status Schedule
Protein Kinases - blood
RNA, Messenger - blood
Ubiquitin-Protein Ligases - blood
Parkin RBR E3 ubiquitin protein ligase (PARK2)
PTEN-induced putative kinase 1 (PINK1)
translocase of outer mitochondrial membrane 40 (TOMM40)
Alzheimer’s disease
apolipoprotein E (ApoE)
methylation
mitochondria
mRNA expression
ISSN:1875-8908, 1875-8908
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Zusammenfassung: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). Assess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD. 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. TOMM40 mRNA expression was significantly lower in AD subjects (0.87±0.18 versus 1.0±0.23, p = 0.005), and PINK1 mRNA expression was higher in AD subjects (1.5±0.61 versus 1.0±0.52, p < 0.001). TOMM40 mRNA expression was significantly correlated with the Mini-Mental State Examination total score (r = 0.290, p = 0.027). There was no expressional change in peripheral APOE mRNA in either AD or control subjects (p = 0.32). 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, p = 0.885), and TOMM40523 polyT genotypes were also not different between AD and control subjects (p = 0.67). 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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1875-8908
1875-8908
DOI:10.3233/JAD-170361