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2016 Grants - Sala Frigerio
Somatic Mutations as Pathogenic Drivers in Sporadic Alzheimer’s Disease
Carlo Sala Frigerio, Ph.D.
Flanders Interuniversity Institute for Biotechnology (VIB)
2016 Alzheimer’s Association Research Fellowship (AARF)
Can genetic modifications of certain brain cells increase the risk for Alzheimer’s disease?
An important focus of Alzheimer’s research involves the search for genetic factors that may be linked to increased risk of developing the disease. Some genetic variations are inherited, while others, called “somatic mutations” can accumulate over an individual’s lifespan. Somatic mutations that only occur in specific cell types may not be detectable using genetic tests of blood or saliva (i.e. the most common testing methods). Dr. Sala Frigerio and colleagues hypothesize that certain somatic mutations in nerve cells may promote brain changes associated with Alzheimer’s disease. It is not yet known if somatic mutations in Alzheimer’s-associated genes are present in most individuals with the disease or how this may impact disease progression.
For their current studies, the investigators will conduct an extensive genetic analysis of brain tissue from people who had Alzheimer’s disease. They expect to identify key dementia-related somatic mutations that occur in certain brain cells. They will then engineer mouse models that develop these specific somatic mutations. The researchers will examine mice at different ages to determine if the somatic mutations promote brain changes associated with Alzheimer’s disease including the accumulation of beta-amyloid ("plaques") and tau ("tangles") and increased levels of inflammation and nerve cell damage.
The results of these studies could shed new light on how certain genetic factors may influence individual variation in the onset or progression of Alzheimer’s disease. A better understanding of these mechanisms could inform the development of novel strategies for the detection or treatment of Alzheimer’s disease.