Influence of APOE ε4 on performance of CSF biomarkers in differentiating clinical Alzheimer's disease

Introduction: Apolipoprotein E epsilon 4 (APOE epsilon 4) bring the higher risk of Alzheimer' Disease (AD). It is essential to evaluate whether the diagnostic performances and critical values of cerebrospinal fluid (CSF) biomarkers are influenced by APOE epsilon 4, which has guiding significance for the clinical practical application. Methods: The differences in CSF biomarkers and their performances between APOE epsilon 4 carriers and non-carriers in distinguishing AD, mild cognitive impairment (MCI) and preclinical AD from normal controls (NCs) were analyzed. The receiver operating characteristic (ROC) curves were generated to compare the area under the curve (AUC) between APOE epsilon 4 carriers and non-carriers, as well as the critical values corresponding Youden Index. Results: In a cross sectional convenience sample of 1610 participants, lower A beta 42 and A beta 42/A beta 40 and higher p-Tau 181/A beta 42 in CSF were observed among APOE epsilon 4 carriers than non-carriers in NC, MCI, and AD groups (P< 0.05). The performance of CSF p-tau/A beta 42 in distinguishing MCI from NC among APOE epsilon 4 carriers was superior to non-carriers [AUC: 0.714 (95%CI: 0.673- 0.752) vs 0.600 (95%CI: 0.564- 0.634), P< 0.001], although it was similar in distinguishing AD from NC between APOE epsilon 4 carriers and non-carriers [AUC: 0.874 (95%CI: 0.835-0.906) vs 0.876 (95%CI: 0.843- 0.904)]. In the longitudinal cohort of 254 participants, the association of CSF A beta 42, A beta 42/A beta 40 and p-Tau181/A beta 42 with cognitive decline were stronger in APOE epsilon 4 carriers compared to non-carriers (P< 0.05). Meanwhile, the critical values were different depending on APOE genotype. Discussion: The CSF level of p-Tau181/A beta 42 was significantly different between APOE epsilon 4 carriers and non-carriers at different stages of AD. The results indicate that the performances of CSF biomarkers are influenced by APOE epsilon 4, which should be considered in the practical application.