School of Medicine

Aging-related genomic culprit found in Alzheimer’s disease

Researchers at Washington University School of Medicine in St. Louis have developed a way to study aged neurons in the lab without a brain biopsy, allowing them to accurately model the effects of aging in the development of late-onset Alzheimer's disease. Shown is a 3D reconstruction of amyloid beta plaque deposition (green) between neurons (red) grown in the lab. These neurons were transformed from human skin cells taken from patients with late-onset Alzheimer's disease.

Researchers at Washington University School of Medicine in St. Louis have developed a way to capture the effects of aging in the development of Alzheimer’s disease. They have devised a method to study aged neurons in the lab without a brain biopsy, an advancement that could contribute to a better understanding of the disease and new treatment strategies.

The scientists transformed skin cells taken from patients with late-onset Alzheimer’s disease into brain cells called neurons. Late-onset Alzheimer’s develops gradually over many decades and only starts to show symptoms at age 65 or older. For the first time, these lab-derived neurons accurately reproduced the hallmarks of this type of dementia, including the amyloid beta buildup, tau protein deposits and neuronal cell death.

By studying these cells, the researchers identified aspects of cells’ genomes — called retrotransposable elements, which change their activity as we age — in the development of late-onset Alzheimer’s disease. The findings suggest new treatment strategies targeting these factors.

The study appears Aug. 2 in the journal Science.

“Sporadic, late-onset Alzheimer’s disease is the most common type of Alzheimer’s disease, representing more than 95% of cases,” said senior author Andrew Yoo, PhD, a professor of developmental biology. “It has been very difficult to study in the lab due to the complexity of the disease stemming from various risk factors, including aging as an important contributor. Until now, we did not have a way to capture the effects of aging in the cells to study late-onset Alzheimer’s.”

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