Protein Active in Fetal Development May Also Protect Against Alzheimer's in Late Life

A new study published yesterday in Nature suggests that a protein thought to be a key element in the brains of fetuses during development may play a critical role in dementia in older people. The protein, known by the acronym REST, is severely depleted in the brains of older adults with Alzheimer's disease (AD) and other dementias, but seems to offer protection against those disorders in healthy older adults, according to research led by Tao Lu, Ph.D., of Harvard Medical School and colleagues. "REST represses genes that promote cell death and Alzheimer's disease pathology and induces the expression of stress response genes," the researchers explain. But "REST is lost from the nucleus" in AD and other dementias, they point out, but was found in levels three times as high in subjects aged 73 and older who did not display dementia symptoms. The protein is barely detectable in young adults, they note.

“This is one of the most fascinating genetic studies in medicine I have seen in a long time," geriatric psychiatrist and former APA President Dilip Jeste, M.D., told Psychiatric News. "Whereas typical genetic investigations focus on genes and proteins that increase the risk of specific diseases, this study examines the role of a protective protein—REST—that appeared to reduce the risk of developing dementia in highly vulnerable older adults with multiple plaques and tangles in their brains.... The suggested reactivation of a fetal protein in old age that may serve to protect against Alzheimer’s disease and other dementias is remarkable. Finally, the reported association of lithium with promoting REST activity may open new windows into our understanding and possible treatment of dementias. It may also shed new light on the cognitive impairment that is commonly seen in people with mood disorders. Obviously, any specific study has its limitations, and much further work is needed to replicate and extend these results. Nonetheless, there is reason for cautious optimism that new discoveries may be on the horizon.”

Read more about Alzheimer's research in the Psychiatric News articles, "High BDNF Levels May Offer Protection Against Alzheimer's" and "Plasma APOE Levels Linked to Dementia Risk."

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