APOE ε4-Allele in Middle-Aged and Older Autistic Adults: Associations with Verbal Learning and Memory

Autism spectrum disorder (ASD) is a neurodevelopmental disability and recent evidence suggests that autistic adults are more likely to develop Alzheimer's disease (Alz) and other dementias compared to neurotypical (NT) adults. The epsilon 4-allele of the Apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alz and negatively impacts cognition in middle-aged and older (MA+) adults. This study aimed to determine the impact of the APOE epsilon 4-allele on verbal learning and memory in MA+ autistic adults (ages 40-71 years) compared to matched NT adults. Using the Auditory Verbal Learning Test (AVLT), we found that epsilon 4 carriers performed worse on short-term memory and verbal learning across diagnosis groups, but there was no interaction with diagnosis. In exploratory analyses within sex and diagnosis groups, only autistic men carrying APOE epsilon 4 showed worse verbal learning (p = 0.02), compared to autistic men who were not carriers. Finally, the APOE epsilon 4-allele did not significantly affect long-term memory in this sample. These findings replicate previous work indicating that the APOE epsilon 4-allele negatively impacts short-term memory and verbal learning in MA+ adults and presents new preliminary findings that MA+ autistic men may be vulnerable to the effects of APOE epsilon 4 on verbal learning. Future work with a larger sample is needed to determine if autistic women may also be vulnerable.

Automated summary

Autistic adults are more prone to Alzheimer's disease and other dementias compared to neurotypical adults. The APOE ε4 allele negatively affects verbal learning and short-term memory in middle-aged and older adults, with potential vulnerability in autistic men.