Multi-gene test predicts Alzheimer's better than APOE E4 alone

New test acts as a genetic risk factor to aid in the identification of preclinical Alzheimer's dementia.

By Amy Wallace

Sept. 25 (UPI) -- Researchers at the University of California, San Francisco, have developed a new test that may be better at predicting Alzheimer's than APOE E4 alone.

The test combines the effects of more than 24 genetic variants that by themselves are only associated with a small risk of developing Alzheimer's disease. The test has been found to be better at predicting which cognitively normal older adults will develop Alzheimer's compared to testing only for the genetic variant APOE E4, which has long been seen as the strongest genetic predictor of Alzheimer's.


The APOE E4 gene is only carried by 10 to 15 percent of the population. The polygenic hazard score, or PHS, developed by UCSF researchers provides risk estimates for the remaining 85 percent to 90 percent of the population who do not carry at least one copy of the APOE E4 gene, but may still be at risk of Alzheimer's.

"Beyond APOE E4 by itself, our polygenic hazard score can identify cognitively normal and mildly impaired older folks who are at greatest risk for developing Alzheimer's-associated clinical decline over time," Chin Hong Tan, a postdoctoral scholar at UCSF, said in a press release.


The PHS test allows researchers to calculate an age-specific risk of developing Alzheimer's disease based on each person's share of 31 genetic variants including APOE E4. The test can make predictions by using genetic data from more than 70,000 people in the National Alzheimer's Coordinating Center database, the International Genomics of Alzheimer's Disease Project and the Alzheimer's Disease Genetics Consortium.

"Unlike other polygenic risk scores, the continuous PHS measure is based on a survival framework and incorporates US-based Alzheimer's incidence rates," said Dr. Rahul Desikan, an assistant professor in the Department of Radiology and Biomedical Imaging at UCSF. "Rather than a diagnostic test, PHS may serve as a genetic 'risk factor' for preclinical Alzheimer's disease."

The study, published Friday in the Annals of Neurology, looked at five years of data on 1,081 people from the NACC and found the PHS test could predict how long before they developed Alzheimer's dementia, how steep their cognitive decline might be, and whether they were APOE E4 carriers.

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Autopsies of patients who developed Alzheimer's showed a higher PHS, even in those who were not carriers of APOE E4, were associated with higher levels of amyloid plaque in the brain, which is a protein aggregate and a hallmark of Alzheimer's disease.


"Our findings have strong implications for disease stratification and secondary prevention trials in Alzheimer's, as well as direct-to-consumer genetic tests, some of which have recently received FDA clearance," said Dr. Anders Dale, a professor of neurosciences and radiology at UC San Diego.

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