Background: APOE-E4 allele (APOE4) increases the risk for sporadic Alzheimer’s disease (AD) and is associated with an earlier onset of dementia. However, studies have shown conflicting results on the association of APOE4 with the age of dementia onset in individuals with autosomal dominant AD (ADAD). Here, we examined the impact of APOE4 on the age-related trajectory of cognitive function in mutation carriers and non-carriers from the Colombian ADAD kindred.
Method: Data were from the world’s largest early-onset ADAD kindred. Analyses included 675 PSEN1 E280A carriers (ages 18 to 75; 141 with an APOE4 allele: APOE4+, and 534 without an APOE4 allele: APOE4-) and 594 non-carriers. The Mini-Mental State Examination (MMSE) was used to assess global cognitive functioning.
Result: Among PSEN1 E280A mutation carriers, lower scores in MMSE began to significantly differentiate APOE4+ from APOE4- at age 45, the estimated mean age of clinical onset in this kindred.
Conclusion: Our findings suggest that age-related changes in cognitive function are accelerated in ADAD mutation carriers who are APOE4+, compared to those who are APOE4-. Future longitudinal studies of PSEN1 mutation carriers are needed to further clarify the impact of APOE4 genotype on rates of cognitive decline and clinical progression.