The Massachusetts Alzheimer’s Disease Center has collected approximately 800 brain samples, providing an extraordinary resource for clinical-pathological correlations for Alzheimer’s disease and other dementias.

This research project involves comparing quantitative phenotypes to genetic markers. In earlier studies, these brain samples were used to study the consequences of inheritance of apolipoprotein E-ε4, and of the ubiquilin 1 risk alleles (described by Dr. Rudolph Tanzi). This research will use 500K chips to do a total genome scan, and also utilize the quantitative phenotypes noted above. 

Such an analysis will give us a window on discovering new genes that impact the rates of progression of patients, the amount of amyloid buildup and deposition, the formation of neurofibrillary tangles, and the amount of neuronal loss.

The research will give us an outstanding pilot data set to test the hypothesis that genetic variations can impact the amount of “reserve” that individuals have against the disease process, and also evaluate genetic influences on rate of progression, amyloid generation, and amyloid deposition.

Researcher: Dr. Bradley T. Hyman, M.D., Ph.D.
MassGeneral Institute for Neurodegenerative Disease

Dr. Hyman directs the Alzheimer’s unit at MIND (Massachusetts Institute for Neurodegenerative Disease), with the goal of understanding the neuropathophysiologic and genetic factors that underlie dementia. The take-off point for Dr. Hyman’s research program involves understanding the neural system failure that underlies cognitive loss in Alzheimer’s, and an appreciation of how genetics impacts pathophysiology. His laboratory also uses transgenic mouse models of Alzheimer’s disease and in vitro systems to examine the roles of presenilin mutations and receptors in neuronal function and on Alzheimer’s related processes.

A recent initiative in Dr. Hyman’s laboratory has been the development of in vivo imaging with 2-photon confocal microscopy. This provides the ability to view neurons in the intact, functioning brain in mice and track the pathological changes that occur during disease processes. His lab has shown that plaques can be reversed by therapeutic application of antibodies.

Dr. Hyman is statewide chair of the Massachusetts Alzheimer’s Association Memory Walk.