<< Back

2023 Alzheimer's Association Research Fellowship (AARF)

Resolving Cellular Resilience and Resistance to Alzheimer’s Disease

Can certain brain cells protect people at risk for Alzheimer’s from dementia-related memory loss and cognitive decline?

Isabel Castanho, Ph.D.
Beth Israel Deaconess Medical Center
Boston, MA - United States


Some individuals who develop risk factors for Alzheimer’s (including beta-amyloid plaques in the brain) manage to avoid memory loss and other cognitive impairments of the disease. These individuals are known as “cognitively resilient.” Many factors contribute to cognitive resilience, including high levels of education and social interaction. Recently, scientists have been exploring how cognitive resilience may be related to the genetic makeup of certain brain cells, and whether these cells are involved in “pathways” (or series of molecular events) that prevent dementia-related risk factors from hindering nerve cell communication and promoting memory loss.

Research Plan

Dr. Isabel Castanho and colleagues will devote their research grant to a study of brain cells linked to cognitive resilience in Alzheimer’s. For this effort, they will examine brain scan and genetic data from older adults enrolled in two large studies of aging. They will also generate and study new brain cell data from centenarian (age 100 and older) participants in a third study of aging. Many people who reach 100 years of age are also cognitively resilient. First, the researchers will identify brain cell populations that protect against cognitive loss in Alzheimer’s, and how these cells may interact with each other to confer that protection. Second, they will use genetic analysis techniques to “map” how these brain cells and brain cell interactions are located across the brain. This experiment will also involve analyzing in detail the small areas of the brain (or “microenvironments”) associated with cognitive resilience. 


Dr. Castanho’s study will shed new light on the cellular and genetic mechanisms underlying cognitive resilience in Alzheimer’s. It could also lead to novel therapies that target resilience-linked cell populations and pathways.  

Back to Top