Novel gene variants that modify the risk of late-onset Alzheimer’s disease discovered

Despite decades of research, genetic factors that predispose individuals to late-onset Alzheimer’s disease(LOAD) are not clearly understood. With a growing elderly population in the U.S. and many other developed countries, there is an urgent need for precise prognostic biomarkers and viable treatment options. Apart from advanced age, variants in the apolipoprotein E (APOE) gene are a strong predictor of disease risk. Those who carry the ε4 variant have a higher risk of developing Alzheimer’s, while those who carry a different variant, ɛ2, are typically protected. Surprisingly, many individuals do not conform to these rules — a puzzle that has confounded researchers. Some people with APOEɛ4 remain disease-free while some APOEɛ2 carriers develop the disease.

Using a novel methodology, researchers at Baylor College of Medicine and Texas Children’s Hospital examined the genomes of these “rule-breaker” individuals, which led to the identification of 216 new gene variants, many previously not suspected to play a role in this disease. This is an exciting first step toward understanding this paradox. The newly-identified biomarkers could potentially be used in the future to refine risk assessment and patient prognosis in APOEɛ2 and APOEɛ4 carrier populations and act as therapeutic targets for this untreatable condition.