It’s well known that the APOE-ε4 variant of the APOE gene places people at greatly increased risk of late-onset Alzheimer’s disease, but only 10 to 15 percent of the population carries the variant, and even some homozygous individuals never develop the disease. It’s clear that APOE-ε4 isn’t the only determinant of Alzheimer’s disease risk. So, what about the 85 to 90 percent of the population without the high-risk variant?
A new study conducted by researchers at the University of California tackles that question with a polygenic hazard score (PHS) that incorporates not only APOE-ε4, but also 31 other genetic variants (1). The test doesn’t diagnose Alzheimer’s, but it can identify individuals without the disease who are most likely to progress to Alzheimer’s dementia as well as determining how steep their cognitive decline is likely to be. Each individual variant alone brings with it only a small risk of disease – but those minor risks are cumulative. Even in patients who carry no APOE-ε4 variants, an elevated PHS was correlated with higher levels of amyloid plaques, steeper cognitive declines, and higher incidences of clinically diagnosed Alzheimer’s disease. The researchers hope that their new test can be used to identify preclinical disease, so that patients can undergo early or even preventive treatment – while they are still in the best possible neurological health.
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References
- CH Tan et al., “Polygenic hazard scores in preclinical Alzheimer disease”, Ann Neurol, 82, 484–488 (2017). PMID: 28940650.
