Investigating the Impact of ABCB1 3435C>T (rs1045642) Variant on Severity and Cognitive Decline in Egyptian Alzheimer’s Disease Patients

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex genetic risk. The ABCB1 gene encodes P-glycoprotein, a blood-brain barrier efflux transporter involved in amyloid-β (Aβ) clearance. Variants in ABCB1 3435C>T (rs1045642) may influence AD susceptibility and severity, but data from Middle Eastern populations remain limited. The objective of the study is to investigate the ABCB1 3435C>T (rs1045642) polymorphism with AD susceptibility, dementia severity, and cognitive impairment in an Egyptian cohort. A case-control study was conducted on 300 subjects, including 150 cognitively healthy controls and 150 clinically diagnosed AD patients. Genotyping for ABCB1 3435C>T (rs1045642) was performed by polymerase chain reaction (PCR). Associations between genotype distribution and AD risk, Clinical Dementia Rating (CDR) scores, and Mini-Mental State Examination (MMSE) categories were analyzed. Logistic regression and Fisher's exact tests were applied to calculate odds ratios (OR) and 95% confidence intervals (CI). The CC genotype was significantly more frequent among controls (64.8%) compared with AD patients (35.2%), whereas the TT genotype predominated in AD (70.5% vs 29.5%). CC carriers were enriched in mild dementia and higher MMSE categories, while TT carriers dominated in severe dementia and lower MMSE groups. Logistic regression confirmed that TT carriers had a 4.4-fold increased risk of AD compared with CC (p < 0.001) and a 13.3-fold higher likelihood of scoring < 20 on MMSE (p < 0.001). The ABCB1 3435C>T (rs1045642) variant significantly influences AD susceptibility and cognitive decline in Egyptians, with TT conferring risk and CC exerting a protective effect. Genotyping may aid risk stratification and monitoring of disease progression.