Genes linked to Alzheimer’s contribute to damage in different ways

Understanding how specific genes trigger injury could lead to treatments Read More

From the WashU School of Medicine News Hub

Multiple genes are implicated in Alzheimer’s disease. Some are linked to early-onset Alzheimer’s, a condition that develops in one’s 30s, 40s and 50s, while others are associated with the more common late-onset form of the disease.

Eventually, all Alzheimer’s patients develop dementia, and their brain cells die. But not all genes linked to the disease contribute to damage in the same way, and understanding the various ways specific genes lead to damage is important to developing potential treatments to prevent or halt Alzheimer’s.

To that end, scientists at Washington University School of Medicine in St. Louis have found that the types of brain cells damaged by the disease vary, depending on the genes involved.

Their findings are published June 8 in the journal Genome Medicine.

“Different genes contribute to Alzheimer’s damage in different ways, and we are working to identify therapeutic targets to prevent that damage,” said senior investigator Carlos Cruchaga, PhD, an associate professor of psychiatry. “Alzheimer’s always leads to neuronal death, but we might identify better targets for therapy if we know how various genes lead to damage.”

The researchers analyzed brain samples from deceased patients with rare and common forms of Alzheimer’s. The tissue banks also included samples from people who did not have the disorder.

As expected, the brains of Alzheimer’s patients generally contained fewer neurons and larger numbers of brain cells called astrocytes. But a closer look showed that the cellular “signatures” in the brains sometimes differed, depending on the genes contributing to the disease.

“Our computer method determined the proportions of each cell type — neurons, astrocytes, oligodendrocytes, microglial cells — and found that specific gene variants were linked to different proportions of these cell types,” said co-investigator Oscar Harari, PhD, an assistant professor of psychiatry.

Using a computerized method, the researchers attempted to differentiate the effects of the genes and identify pathways that might be therapeutic targets.

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Posted on June 7, 2018
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