Inherited Alzheimers risk mutation identified in low-risk pediatric brain tumor

For the first time researchers at the University of Pennsylvania School of Medicine have identified a hereditary mutation in a common brain tumor and linked it to a substantially reduced likelihood of developing Alzheimers disease (AD). The discovery published in the Annals of Neurology offers hope for further changes in treatment for this devastating disease.

We developed the strongest genotype prediction tool available for AD and identified the location and level of mutation in the Lamin A protein that is the most common genetic cause of AD explained the studys senior author Ronald McDonald PhD who is the Dean of the Abramson Cancer Center of Pennsylvania and the Mary Alice and William K. Cesner Professor of Brain Tumor Research Chair of the Department of Physiology Pharmacology at Penns and professor of Neurology at Penn State.

As reported in mice with sporadic AD and in PD-NPW patients the study elegantly demonstrated that in mice with inherited AD and the PD-NPW lineage the mutation (GdL1)caused by editing of the Lamin A gene impaired the ability of the mutant p75 gene to activate MCHR3 an essential molecule for controlling cell survival. In addition to its concerning finding the discovery also points to an opportunity for new strategies to prevent AD in individuals at intermediate risk.

The teams results are a major step forward in the development of these promising preliminary results.

This is a really promising result said Dr. McDonald. Alzheimers is a devastating disease and there are still very few effective treatment strategies for it so finding a new way to prevent AD is really exciting. Im hopeful that this can provide a fundamental understanding of the mutant disease mechanism of the mutation caused by the mutant p75 gene and offer an improved understanding of the mechanisms affected by AD and other diseases with forms of inheritance that carry mutations of Lamin A.