The interplay of APOE genotype, plasma levels, and cognitive functions in middle-aged adults with a parental history of Alzheimer’s disease

BACKGROUND: Family history and APOE ε4 carriage represent the strongest non-modifiable Alzheimer's disease (AD) risk factors after advancing age. Early identification of cognitive markers in individuals at risk is essential for effective intervention strategies. OBJECTIVES: To assess global cognition and its executive function subset in middle-aged offspring of AD patients versus controls, and to examine the influence of the Apolipoprotein E (APOE) ε4 allele and the potential of plasma APOE levels as a peripheral biomarker for cognitive health. METHODS: In this case-control study, 80 clinically asymptomatic subjects (40 offspring of AD patients and 40 matched controls with no parental history of dementia) underwent comprehensive cognitive and executive function assessments, APOE genotyping, and plasma level measurements. RESULTS: Offspring scored significantly lower on the Montreal Cognitive Assessment (MoCA), indicating early cognitive impairments despite being clinically asymptomatic. The APOE ε4 allele was more prevalent in the offspring group, although plasma APOE levels did not differ significantly between groups. A positive correlation was observed between plasma APOE levels and cognitive performance. CONCLUSION: Middle-aged offspring of AD patients exhibit early cognitive vulnerabilities and a higher prevalence of the APOE4 genotype. These findings emphasise the importance of early monitoring and potential interventions for individuals at genetic risk for AD.