Background Previous studies have shown contradictory findings on if the APOE gene is associated with sleep apnea. Thus, the goal of this study is to examine the relationship between the APOE gene and sleep apnea and investigate whether levels of amyloid beta in cerebrospinal fluid (CSF) depend on sleep apnea and/or APOE gene. Method Data was obtained from the National Alzheimer’s Coordinating Center (NACC). We restricted participants to those who were enrolled at or after 2015 due to availabilities of sleep apnea measurements and with normal cognition status at enrollment. CSF sample data for a subset of these participants were merged to initial visit data by subject ID and year of visit. Logistic regression was used to investigate the association between sleep apnea and APOE and backward elimination was used to identify a final model. T‐tests were used to compare the mean levels of CSF amyloid beta between APOE gene groups and between sleep apnea groups, respectively. Result Of a total of 1630 subjects identified to meet criteria, 3.83% participants had sleep apnea and are APOE ε4 carriers, 26.87% did not have sleep apnea and are APOE ε4 carriers, 9.88% had sleep apnea and are APOE ε4 non‐carriers, 59.45% did not have sleep apnea and are APOE ε4 non‐carriers. Logistic regression showed that sleep apnea was not significantly associated with APOE gene after adjusting age, gender and BMI. The mean levels of CSF amyloid beta among APOE ε4 carriers (mean± SD: 414.7±241.7) were lower than APOE ε4 non‐carriers (mean± SD: 500.9±150.5), and the mean levels of CSF amyloid beta among sleep apnea subjects (mean± SD: 434.6±90.1) were lower than subjects without sleep apnea (mean± SD: 504.9±194.3). However, the differences were not statistically significant. Conclusion In this study, sleep apnea was not significantly associated with APOE in the NACC sample and the mean levels of CSF amyloid beta did not depend on sleep apnea or APOE gene in cognitively normal subjects.