Polygenic risk score may identify Alzheimer disease risk in younger populations

For the first time, an international team of scientists, led by researchers at University of California San Diego School of Medicine, have determined that an Alzheimer disease polygenic risk score can be used to correctly identify adults with mild cognitive impairment who were only in their 50s. Mild cognitive impairment is considered a precursor to Alzheimer disease.

Findings were published in the February 27 online edition of Molecular Psychiatry.

The Alzheimer disease polygenic risk score was created from genome-wide association studies of Alzheimer disease with a combination of genes weighted according to the association of single nucleotide polymorphisms (SNPs) with Alzheimer disease. SNPs are variations of a single nucleotide or DNA-building block that occur at a specific position in the genome. There is some SNP variation in genomic information in all humans, which affects individual susceptibility to disease.

"Current studies of the Alzheimer disease polygenic risk score typically occur in adults in their 70s, but the Alzheimer disease pathological process begins decades before the onset of dementia," said William S Kremen PhD, professor of psychiatry and co-director of the Center for Behavior Genetics of Aging at UC San Diego School of Medicine. "By focusing on a younger population with cognitive impairment, we may be better able to identify patients for critical early interventions and clinical trials."

Kremen and team found that someone with an Alzheimer disease polygenic risk score in the upper quartile was 2.5 to 3 times more likely to have mild cognitive impairment than someone with a score in the lowest quartile. Signs of mild cognitive impairment may include difficulty with word recall, forgetting appointments, or often losing personal belongings. The type of mild cognitive impairment most associated with memory loss is called amnestic mild cognitive impairment.

According to the National Institute on Aging, more people with mild cognitive impairment than those without it go on to develop Alzheimer disease. Approximately eight of every 10 persons who fit the definition of amnestic mild cognitive impairment develop Alzheimer's disease within 7 years.

"Our research team found that the polygenic score could differentiate individuals with mild cognitive impairment from those who were cognitively normal," said Kremen. "We also noticed that for study participants who had cognitive deficits other than memory problems, diabetes was 3-fold more likely."

Kremen added that while this test is not yet available to primary care physicians, it may be an important tool to aid researchers in predicting mild cognitive impairment and Alzheimer disease, and, eventually, reducing the number of future cases.

"The Alzheimer's Association and others have modeled how the impact of delaying the onset of Alzheimer disease by 5 years could reduce the number of cases by nearly 50% by 2050. We want to do what we can to make this projection a reality," said Kremen.

Data for this study were collected from 1,329 men who participated in the Vietnam Era Twin Study of Aging (VESTA.). VESTA constitutes a national sample comparable to U.S. men in their age range with respect to health and lifestyle characteristics. Approximately 90% of subjects in this analysis were in their 50s. Diagnosis of Alzheimer disease was based on the Jak-Bondi actuarial/neuropsychological approach.

Source: News Release
University of California - San Diego
March 5, 2018