Association of APOE ε4 with cerebrospinal fluid protein and amyloid-β ₄₂ levels in Alzheimer's disease

Background Alzheimer's disease (AD) is a neurodegenerative disease, with APOE ε4 as the most common genetic risk factor. This protein has been implicated in amyloid-β peptide (Aβ)-mediated pathological processes in patients with AD. However, the mechanism by which APOE ε4 regulates cerebrospinal fluid (CSF) protein levels and Aβ 42 concentration in CSF during the pathogenesis of AD has not been clarified. Objective To determine whether APOE ε4 contributes to the pathogenesis of AD by altering Aβ 42 concentrations and protein levels in CSF. Methods A total of 228 AD patients were enrolled and assigned into the APOE non-ε4 carrier group (146 patients) and the APOE ε4 carrier group (82 patients). The concentration of Aβ 42 and protein levels in CSF, as well as APOE genotypes were quantified. Subsequently, the association of APOE ε4 with CSF biomarkers was explored through multiple logistic regression analysis. Results In APOE ε4 carriers, CSF Aβ 42 ( p = 0.016) and the protein ( p = 0.040) levels in CSF were lower compared with levels in the non-carrier group. Moreover, APOE ε4 carriage was associated with lower levels of CSF Aβ 42 (odds ratio 0.998, 95% confidence interval 0.995–1.000, p = 0.048) and CSF protein (odds ratio 0.004, 95% confidence interval 0.000–0.224, p = 0.007) in APOE ε4 carriers. Conclusions APOE ε4 modulates the CSF protein levels and CSF Aβ 42 concentrations in AD patients. This indicates that the APOE ε4 genotype and CSF protein levels may help monitor the progression of AD.