CSF A42 and tau biomarkers in cognitively unimpaired A- middle-aged and older APOE 4 carriers

This study aimed to determine the relationship between the apolipoprotein E (APOE) & epsilon;4 allele and cerebrospinal fluid (CSF) and neuroimaging biomarkers of Alzheimer's disease, and cognition in cognitively unimpaired (CU) middle-aged adults (n = 82; Mage = 58.2), and in A & beta;-CU older adults (n = 71; Mage = 71.8). A & beta;-CU middle-aged & epsilon;4 carriers showed lower CSF A & beta;42 levels, higher levels of CSF total tau (t-tau) and neurofilament light (NfL), and poorer cognitive performance compared to noncarriers (Cohen's d: 0.30-0.56). In A & beta;-CU older adults, & epsilon;4 carriers also had lower CSF A & beta;42 levels and higher levels of CSF t-tau and p-tau181, compared to noncarriers (Cohen's d: 0.65-0.74). In both A & beta;-middle-aged and older adults, hippocampal and total brain volume were equivalent between & epsilon;4 carriers and noncarriers. In A & beta;-CU middleaged adults, APOE & epsilon;4 is associated with decreased levels of A & beta;, increased tau and NfL, and poorer cognition. Similar relationships were observed in A & beta;-CU older adults. These results have implications for understanding clinicopathological relationships between APOE & epsilon;4 and the emergence of cognitive and biomarker abnormalities in A & beta;-adults.& COPY; 2023 Elsevier Inc. All rights reserved.