Rare genetic variants and their protective effects in individuals with familial Alzheimer's disease

Yakeel T. Quiroz, PhD
Paul B. and Sandra M. Edgerley MGH Research Scholar 2020-2025
Departments of Psychiatry and Neurology, Massachusetts General Hospital
Associate Professor of Psychology, Harvard Medical School

My research focuses on identifying brain changes linked to increased risk or protection for Alzheimer's disease dementia.

We work with individuals who belong to the world's largest family with autosomal-dominant Alzheimer's disease due to a single mutation in the Presenilin-1 (PSNE1) gene.

This opportunity allows us to examine individuals genetically determined to develop Alzheimer's, even before they have signs of cognitive impairment.

My lab uses clinical, cognitive, brain imaging and genetics to examine brain function and in vivo pathology of mutation carriers, decades before they develop any symptoms of the disease.

Our recent work has focused on examining individuals from this family who did not develop dementia at the estimated age of clinical onset.

Our latest results revealed that a rare mutation in the apolipoprotein E (APOE) gene may confer protection against familial dementia, as it seems to have prevented memory loss in an individual who carried the PSEN1 mutation.

My work will provide new understanding of how brain pathology (amyloid and tau buildup) impacts memory function very early in the disease process, and its role in subsequent neuronal death and cognitive decline.