Rare Gene Variant may Shield From Devastating Form of Early Alzheimer’s

A newly discovered genetic variant protects against a particularly devastating form of early Alzheimer’s disease, raising scientists’ hopes of finding treatments that can prevent or slow the progression of this and other forms of the disease. The discovery is only the second gene variant reported to protect against autosomal dominant Alzheimer’s disease (ADAD), a form of Alzheimer’s caused by an inherited genetic mutation. People with ADAD begin to show signs of dementia in their mid-40s and rarely survive past the age of 60, study co-author Dr. Joseph Arboleda-Velasquez, a biomedical researcher at Harvard University, told Live Science.

The patient at the heart of the new study was a male member of a Colombian family that researchers have been following for a long time because they’re known carriers of the genetic mutation that causes ADAD. This man carried that gene, but instead of succumbing to early dementia, he remained healthy into his late sixties and developed only mild Alzheimer’s disease by age 72. He died at 73 years old of non-dementia-related causes.

It was just really remarkable that he made it that far, despite the odds,” Arboleda-Velasquez said.

To find out how, Arboleda-Velasquez and his colleagues sequenced the man’s genes and came up with a list of genetic variants, or specific versions of genes, that might have been protective. One gene, RELN, popped out as intriguing because the protein it codes for binds to the same cellular receptors as the protein made by a well-known gene called APOE. One variant of the APOE gene raises the risk of Alzheimer’s by partially driving the formation of amyloid plaques, clusters of misfolded proteins considered to be a hallmark of Alzheimer’s.

The researchers studied the effects of the RELN gene in cells in lab dishes and in mice and discovered that the variant the man carried actually made the protein that RELN codes for bind more tightly to its receptor. This effect seems to help the RELN protein stabilize the protein tau, which can form tangles in the brain that serve as another tell-tale sign of Alzheimer’s.

The patient had reduced tau tangles in many parts of his brain compared to other Alzheimer’s patients, but some portions still showed tau pathology. Delving deeper into the gene variant and how it protects against early-onset Alzheimer’s is the crucial next step, said Dr. Kenneth Kosik, a neurologist at UC Santa Barbara who studies ADAD but who was not involved in the current research.

Source: https://www.livescience.com/