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2013 Mentored New Investigator Research Grant to Promote Diversity (MNIRGD)

AD Risk Prediction, Cognitive Decline & Gene Regulation at the TREM2 locus

Minerva Carrasquillo, Ph.D.
Mayo Clinic Jacksonville
Jacksonville, FL - United States

In recent years, much Alzheimer’s disease research has focused on determining genetic risk factors for the disorder. A better understanding of the disease’s genetic mechanisms could lead to improved methods of Alzheimer’s diagnosis and prevention. In preliminary studies, Minerva Carrasquillo, Ph.D., and colleagues have identified a variant (unusual form) of a normal gene called TREM2, which may increase the risk of Alzheimer’s disease in people. TREM2 exists within a cluster of genes called TREM genes, and variants of other TREM genes (including TREM1, TREML1, TREML2 and TREML4) may also promote brain dysfunction and dementia.

For this grant, Dr. Carrasquillo and colleagues hope to learn more about how TREM genes and Alzheimer’s risk are linked. First, they will search for novel dementia-related TREM variants by (1) analyzing autopsied brains of people who had Alzheimer’s disease and (2) searching through public databases of genes that have already been identified. Once candidate TREM genes have been determined, the researchers will examine brain data from several larger groups of people — people with and without Alzheimer’s — to confirm whether their candidate genes are typically found in the Alzheimer’s brain. They will also assess whether the genes are associated with declines in cognition (brain function) over time and with the development of mild cognitive impairment, a condition that may precede Alzheimer’s.

Dr. Carrasquillo’s group will then look for biological mechanisms that may underlie the links between TREM variants and Alzheimer’s disease. Specifically, they hope to identify minute changes in transcription that are characteristic of these genes. Transcription is the process by which a gene is turned on so it can be converted into a protein. Such changes may help explain how harmful TREM genes promote Alzheimer’s-like abnormalities in the brain. Overall, the results of Dr. Carrasquillo’s effort could shed new light on the hereditary aspects of dementia. They could also lead to novel genetic methods for diagnosing Alzheimer’s at an early stage.

This project is sponsored by the Alzheimer's Association Research Roundtable

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