Impact of APOE ε4 allele on familial aggregation and cerebrovascular disease in Alzheimer’s Dementia: A cross‐sectional pilot study from India

Abstract

AbstractBackgroundThe ε4 variant of the apolipoprotein E gene (APOE4) is associated with the risk of Alzheimer’s dementia (AD). Previous studies have reported APOE4 status association with familial loading and vascular changes in AD. With a diverse ethnic population, and high rates of metabolic syndromes, the consequences of being a carrier of the APOE4 polymorphism needs further exploration in Indian context.MethodPatients (N = 452) diagnosed to have AD, including 75 with a family history of AD in first‐degree relatives [‘familial’ AD (FAD)] and others without a significant family history [‘sporadic’ AD (SAD)], under evaluation at a tertiary hospital in India are described. All patients were assessed using Clinical Dementia Rating scale (CDR), Hindi Mental Status Examination (HMSE), Everyday Abilities Scale for India (EASI), Neuropsychiatric Inventory (NPI), and the Hachinski Ischemic Scale (HIS), along with detailed clinical evaluation. Blood samples were collected from AD patients, and 456 matched healthy controls for APOE genotyping using Polymerase Chain Reaction restriction fragment length polymorphism.ResultsThe ε4 allele frequency was 22.57% and 9.65% among AD patients and healthy controls. APOE4 carrier status was noted in 52% of FAD, 38.46% of SAD patients, and was a significant risk factor for FAD with an odd’s ratio (OR) of 1.73 (95% confidence interval (CI):1.04‐2.9, p = 0.03). The presence of APOE4 did not have a significant association with metabolic comorbidities (p = 0.54). Furthermore, APOE4 status was a negative predictor for cerebrovascular disease among all AD patients (OR: 0.32, 95% CI: 0.12‐0.71, p = 0.008).ConclusionAPOE4 allele has a positive association with familial aggregation and a negative association with cerebrovascular adversities in AD. The effect of APOE4 polymorphism on the clinical manifestation of AD in Indian population is unclear and needs further evaluation.