Apolipoprotein E ε4 and ε3 alleles associate with cerebrospinal fluid tau and cognition in the presence of amyloid-𝜷 in mild cognitive impairment but not in Alzheimer’s disease

Apolipoprotein E is the most well-established genetic risk factor for Alzheimer’s disease. However, the associations of apolipoprotein E with tau pathology and cognition remain controversial. The research checks the hypothesis that the relationships between apolipoprotein E alleles and cerebrospinal fluid tau and cognition differ in persons with and without significant amyloid-β deposition. We divided 1119 subjects into cognitively normal (n = 275), mild cognitive impairment (n = 629), and Alzheimer’s disease (n = 215), and these subjects were from the Alzheimer’s Disease Neuroimaging Initiative database. Linear regression models were used to compare the relationships of apolipoprotein E alleles with cerebrospinal fluid tau and cognition in persons with significant amyloid-β deposition relative to individuals without significant amyloid-β deposition. The associations of apolipoprotein E ε4 and ε3 with total tau (T-tau), phosphorylated tau (P-tau), and Alzheimer’s disease assessment scale was significantly substantial among participants with significant amyloid-β deposition. Stratified analyses showed that apolipoprotein E ε4 related to increased concentrations of T-tau, P-tau, and Alzheimer’s disease assessment scale and apolipoprotein E ε3 associated with decreased concentrations of T-tau, P-tau, and Alzheimer’s disease assessment scale in mild cognitive impairment participants with significant amyloid-β deposition, but not in Alzheimer’s disease. Our study shows that the presence of apolipoprotein E ε4 and ε3 alleles is related to tau pathology and cognitive impairment in the presence of amyloid-β in mild cognitive impairment, but not in Alzheimer’s disease. This work indirectly provides additional evidence that apolipoprotein E and amyloid-β may not have a role in modulating clinical Alzheimer’s disease, and apolipoprotein E ε3 may be supposed to be protective to mild cognitive impairment.