New Way to Study Alzheimer's Disease

This image illustrates neurons derived from stem cells of a living patient with a genetic predisposition to Alzheimer’s disease. Neuronal protein is shown in green. Red depicts a subset of neurons affected in the disease process.

Using cells from blood relatives with familial Alzheimer’s disease (AD), a team of researchers at Brigham and Women’s Hospital (BWH) has been able to study the underlying causes of AD and develop new ways to test treatment approaches.

People with familial AD have a genetic predisposition that leads to early development of the disease. More than 200 different mutations are associated with familial AD. Depending on the mutation, patients with familial AD can begin exhibiting symptoms as early as their 30s and 40s.

“Our research using human cells affected by AD has been limited to tissue samples from patients who have already died from the disease,” says Dr. Tracy L. Young-Pearse, corresponding author of the study recently published in Human Molecular Genetics and an investigator in the BWH Center for Neurologic Diseases. “AD is characterized by the presence of amyloid-beta protein plaques and Tau protein tangles, but observing living cell behavior and understanding the role of these abnormal protein deposits and tangles and their relationship has been challenging.”

The cells for the study were obtained from skin biopsies provided by a 57-year-old father with AD and his 33-year-old-daughter, who does not currently show any symptoms of AD. The BWH researchers submitted the skin biopsies to the Harvard Stem Cell Institute, where the cells were converted into induced pluripotent stem cells (or iPSCs). Dr. Young-Pearse’s lab then directed the stem cells to develop into neurons related to a region of the brain that is responsible for memory and cognitive function.

“The living cells provided for this study enabled us to investigate the actual disease process and test the effects of newer treatments,” said Dr. Young-Pearse.

Experimental treatments currently being evaluated for AD use antibodies to try to neutralize the harmful effects of amyloid-beta. The antibodies can bind to and clear the amyoid-beta peptide from the brain. This study is the first of its kind to examine the effects of antibody therapy on human neurons derived directly from patients with familial AD.

“Amyloid-beta immunotherapy is a promising therapeutic option in AD, if delivered early in the disease process,” said Dr. Young-Pearse. “Our study design, based on actual patients, may be useful in testing and comparing amyloid-beta antibodies, as well as other emerging therapeutic strategies in treating AD.”

– Jessica F.

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