The roles of apolipoprotein E ε4 on neuropathology and neuroinflammation in patients with Alzheimer's disease

Background: Apolipoprotein E ( APOE) ε4 is one of the greatest risk factors for sporadic Alzheimer's disease (AD), but the relationship between APOE ε4 and different cognitive domains, pathological proteins and neuroinflammatory factors in cerebrospinal fluid (CSF) is still unclear. This study aimed to explore the roles of APOE ε4 on the neuropathology and neuroinflammation in AD patients. Methods: AD patients were divided into the APOE ε4 carrier and the APOE ε4 non-carrier groups according to APOE genotypes. Demographic information, cognitive function, the levels of neuropathological proteins and neuroinflammatory factors in CSF were compared between the two groups, and the correlations among the above-mentioned variables were subsequently analyzed. Results: APOE ε4 carriers had significantly worse performances in overall cognitive function and individual cognitive domains ( P < 0.05) than the non-carriers. β amyloid protein (Aβ) 1-42 level from the APOE ε4 carrier group was significantly lower than that from the non-carrier group ( P = 0.023), which was associated with worse cognitive function. The nitric oxide (NO) level was significantly elevated in the APOE ε4 carrier group compared to the non-carrier group ( P =0.016), which was significantly and positively correlated with the Trail Making Test (TMT)-A-time (r = 0.21, P = 0.026) and TMT-B-time (r = -0.38, P < 0.01). Conclusion: APOE ε4 is associated with poorer cognitive function of AD, particularly the early symptoms of memory, language and attention. APOE ε4 is associated with lower Aβ 1-42 level in CSF, and the more numbers of APOE ε4 are carried, the lower level of Aβ 1-42 is measured. APOE ε4 is associated with elevated NO level in CSF, which is linked to the impaired cognitive domains of attention and executive function.