Results of an international collaboration across teams in Spain, Switzerland, and Germany report a new association between the PM20D1 gene and Alzheimer’s disease (AD). The comprehensive study combined genetic and epigenetic approaches from human tissue samples, as well as follow ups using mouse models.

This is an example of cells of a patient with advanced Alzheimer’s with an altered PM20D1 gene. [IDIBELL]

The results demonstrate that enhancing PM20D1 expression in AD mice reduced AD-related pathologies, whereas depleting PM20D1 promoted AD-related pathologies. This suggests that given a specific genetic background, PM20D1 contributes to neuroprotection against AD.

Dr Manel Esteller, one of the studies co-authors, had the following to say, “This variation is associated with the loss of activity of a neuroprotective gene called PM20D1; whoever possesses the variation has a greater probability of suffering from Alzheimer’s disease, so people carrying these variants could be excellent candidates for clinical prevention trials of the disease in the future”

Speaking more generally on the study, Esteller explained, “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.”

“The results obtained demonstrate the need for international scientific collaboration, mixing the different areas of experience in epigenetics, genetics, bioinformatics and neurosciences of each group. We are looking at an example of the usefulness of multidisciplinary research to tackle diseases as complex and devastating as dementia”

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