ABSTRACTAutism spectrum disorder (ASD) is a neurodevelopmental condition associated with social communication challenges and restrictive and repetitive behaviors [2]. Despite known lifelong challenges, understanding of cognitive and brain aging with ASD is lacking. Middle-aged adults with ASD have a higher chance of developing Alzheimer’s disease (Alz) and other dementias compared to neurotypical (NT) adults [12]. Apolipoprotein E (APOE) is a lipid transport protein involved in neuronal repair and cholesterol transport and is the strongest genetic risk factor for Alz [22]. Others demonstrated that individuals with ASD are more likely to carry the APOE ε4-allele [21]. This study aimed to determine if the APOE ε4-allele negatively impacts verbal learning and memory in ASD compared to NT adults. Participants were intellectually able 76 middle-age and older adults (MA+) between the ages of 40-71, including 35 with ASD [mean age=53.06 (±8.91)] and 41 NT adults [mean age=53.90 (±8.44)]. APOE allelic distribution was determined from salivary samples via polymerase chain reaction amplification and genotyped on a tapestation. The Auditory Verbal Learning Test (AVLT) variables were short-term memory, long-term memory, and total learning. There was a main effect of APOE ε4 for short-term memory and verbal learning, with ε4 carriers performing worse across diagnosis groups. For verbal learning, sex was a significant predictor. So, exploratory analyses separating diagnosis groups by sex were conducted. Only males with ASD were found to be carrying APOE ε4 associated with reduced verbal learning (p=0.02). Finally, the APOE ε4-allele did not significantly affect the participants’ long-term memory. These findings suggest that the APOE ε4-allele negatively impacts short-term memory and verbal learning in MA+ adults, and that autistic men may be particularly vulnerable to the effects of APOE ε4 on verbal learning. This study is the first to incorporate ASD in APOE’s association with cognition and investigate how sex differences impact memory function. Future research is needed to replicate these findings using a larger sample size to further understand how the ε4-allele affects memory function trajectories in MA+ ASD as they grow older.