DNMT3A Moderates Cognitive Decline in Subjects with Mild Cognitive Impairment: Replicated Evidence from Two Mild Cognitive Impairment Cohorts

Abstract

Epigenetic dysregulation has been associated with cognitive decline and Alzheimer’s disease. The present study investigated associations between common SNPs in genes regulating DNA methylation and age-related changes in cognitive decline in two independent prospective cohorts of patients suffering from mild cognitive impairment. An association between the rs1187120 SNP in DNMT3A and annual decline in cognitive functioning was discovered and replicated, suggesting that DNMT3A moderates cognitive decline in subjects with mild cognitive impairment.

Keywords::

• aging
• DNA methylation
• DNMT3A
• epigenetics
• MCI
• mild cognitive impairment
• SNP

Financial & competing interests disclosure

Funds have been provided by the Internationale Stichting Alzheimer Onderzoek, grant number 07551 and 11532 (DLA van den Hove), by the ISAO grant number 09552, and the Netherlands Organization for Scientific Research (NWO, Veni Award 916.11.086) (BPF Rutten). The DESCRIPA study was supported by the European Commission 5th Framework Programme contract number QLK-6-CT-2002-02455. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The local Medical Ethical Committee in each centre approved the study. Subjects were asked to provide a written informed consent except in two centers, in which the study was considered to be regular patient care and no specific consent was needed.

Additional information

Funding

Funds have been provided by the Internationale Stichting Alzheimer Onderzoek, grant number 07551 and 11532 (DLA van den Hove), by the ISAO grant number 09552, and the Netherlands Organization for Scientific Research (NWO, Veni Award 916.11.086) (BPF Rutten). The DESCRIPA study was supported by the European Commission 5th Framework Programme contract number QLK-6-CT-2002-02455. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.