Clinical correlates of APOE ε4 homozygosity in Alzheimer's dementia: findings from an Indian cohort.
AIM The apolipoprotein E ε4 (APOE ε4) allele is a well-established genetic risk factor for Alzheimer's disease (AD), with a gene-dose effect, but its prevalence and clinical correlates in remain underexplored in South Asians. We examined APOE ε4 homozygosity and its clinical correlates in Indian cohort. PATIENTS AND METHODS We analyzed APOE genotype data from 393 patients with AD and 850 age-matched healthy controls from India. Variables included family history of dementia, age at onset, behavioral and psychological symptoms of dementia (BPSD), comorbidities (Diabetes and Hypertension), and severity on the Hindi Mental Status Examination (HMSE) and Clinical Dementia Rating (CDR) scale. RESULTS APOE ε4 allele frequency was higher in patients with AD (25%) than controls (9%); homozygosity was also more frequent among patients (5% vs 1%; X2 = 103.48, p < 0.001). Homozygosity was associated with family history of dementia, [Odds Ratio (OR) 4.03, 95% CI 1.46-11.10, p = 0.007], consistent on Firth analysis, but not with age at onset, duration, severity, BPSD, or comorbidities. CONCLUSION In this Indian cohort, APOE ε4 homozygosity reflects increased susceptibility and familial aggregation of AD but does not confer a more severe or distinct phenotype, suggesting ancestry- specific expression of APOE ε4 gene-dose effects.