2023 Alzheimer's Association Research Fellowship (AARF)
Neuroimage-Genetic Integration to Investigate Risk and Resilience in AD
Can a novel method of analyzing genetic and brain scan data help clarify how certain genes impact Alzheimer’s risk?
Ibai Diez, Ph.D.
Massachusetts General Hospital
Boston, MA - United States
Background
Genes play complex roles in late-onset Alzheimer’s disease (LOAD), the most common form of the disorder. One gene variation called APOE-e4, which provides instructions for making ApoE protein, is thought to promote LOAD in some populations. However, there are numerous other gene variations that likely affect Alzheimer’s risk. In recent years, for example, large-scale genome-wide association studies (or GWAS), which analyze genetic information from large groups of individuals, have identified 98 LOAD-related genetic regions (or “loci”) on chromosomes, the organized structures of genetic material (DNA) in a cell. Scientists are now exploring these loci to find novel Alzheimer’s genes.
Research Plan
Dr. Ibai Diez and colleagues will examine Alzheimer’s genetic loci to look for genetic factors that either promote dementia risk or are protective against that risk. Their effort will involve genetic and brain scan data from participants in four large studies of aging. Using a novel method of analyzing this genetic and imaging data together, they will assess how genes in various risk loci may impact the progression of Alzheimer’s differently in different individuals. For example, they will explore how various genes may be linked to brain cell loss or the accumulation of beta-amyloid and tau proteins in different areas of the brain. They will also analyze the genetic loci to look for gene variations that may be protective against LOAD in different people.
Impact
Results from Dr. Diez’s study could improve our understanding of the diverse nature of Alzheimer’s disease – and the genetic factors underlying this diversity. They could also lead to novel, individually targeted genetic therapies for the disease.