PM20D1 gene associated with Alzheimer’s disease incidence, research finds

As per a recent article published in Nature Medicine, a recent research conducted has identified an association of the peptidase M20-domain-containing protein 1 (PM20D1) with the incidence or occurrence of Alzheimer’s disease.

The article further states that the chances to develop Alzheimer’s disease (AD) result from a combination of genetic and non-genetic risk factors, the latter likely being mediated by epigenetic mechanisms. In the past, genome-wide association studies (GWAS) have identified an important number of risk loci associated with AD pathology, but a causal relationship remained difficult to establish. In contrast, locus-specific or epigenome-wide association studies (EWAS) have revealed site-specific epigenetic alterations, which provide mechanistic insights for a particular risk gene but often lacked the statistical power of GWAS4. Combining both approaches, the study reports a previously unidentified association of the peptidase M20-domain-containing protein 1 (PM20D1) with AD. The researchers found that PM20D1 is a methylation and expression quantitative trait locus coupled to an AD-risk associated haplotype, which displays enhancer-like characteristics and contacts the PM20D1 promoter via a haplotype-dependent, CCCTC-binding-factor-mediated chromatin loop. Furthermore, PM20D1 is increased following AD-related neurotoxic insults at symptomatic stages in the APP/PS1 mouse model of AD and in human patients with AD who are carriers of the non-risk haplotype. In line, genetically increasing or decreasing the expression of PM20D1 reduces and aggravates AD-related pathologies, respectively. These findings suggest that in a particular genetic background, PM20D1 contributes to neuroprotection against AD.

“Over the last seven years, we have created a detailed map of the epigenetic alterations that occur in the brain of people affected by Alzheimer’s and other dementias such as those associated with the so-called Lewy bodies or Parkinson’s disease. That allowed us to collaborate with Dr Johannes Gräff’s group in Lausanne, who noticed how one of the molecular lesions we had discovered was caused by inheriting a variation in the DNA sequence”- states Dr. Manel Esteller, co-author of the Nature Medicine study.

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News Source: https://www.eurekalert.org/pub_releases/2018-05/ibri-sda051418.php

Image Source: http://www.jdfaf.org/news-blog/2016/12/1/new-research-project-to-examine-the-role-of-microglia-in-alzheimers-disease-using-cellular-reprogramming