Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| [b] Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China
Correspondence:
[*]
Correspondence to: Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China. Tel.: +86 0532 88905915; E-mail: dr.tanlan@163.com.
Note: [1] The available data used in preparation for this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: https://adni.loni.usc.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Abstract: Background:The APOE genotype has emerged as the major genetic factor for AD but differs among different alleles. Objective:To investigate the discrepant effects of APOE genotype on AD cerebrospinal fluid (CSF) biomarkers. Methods:A total of 989 non-demented ADNI participants were included. The associations of APOE ɛ2 and APOE ɛ4 with CSF biomarkers were investigated using linear regression models. Interaction and subgroup analyses were used to investigate the effects of sex and age on these associations. Furthermore, we used mediation analyses to assess whether Aβ mediated the associations between APOE genotypes and tau. Results:APOE ɛ2 carriers only showed higher Aβ levels (β [95% CI] = 0.07 [0.01, 0.13], p = 0.026). Conversely, APOE ɛ4 carriers exhibited lower Aβ concentration (β [95% CI] = –0.27 [–0.31, –0.24], p < 0.001), higher t-Tau (β [95% CI] = 0.25 [0.08, 0.18], p < 0.001) and higher p-Tau (β [95% CI] = 0.31 [0.25, 0.37], p < 0.001). Subgroup analysis showed that APOE ɛ2 was significantly positively associated with Aβ only in females (β [95% CI] = 0.12 [0.04, 0.21], p = 0.005) and older people (β [95% CI] = 0.06 [0.001, 0.12], p = 0.048). But the effects of APOE ɛ4 were independent of gender and age. Besides, the associations of APOE ɛ4 with t-Tau and p-Tau were both mediated by baseline Aβ. Conclusions:Our data suggested that APOE ɛ2 could promote Aβ clearance, while the process could be modified by sex and age. However, APOE ɛ4 might cause the accumulation of Aβ and tau pathology independent of sex and age.
Keywords: Age interaction, Alzheimer’s disease, amyloid-β
, APOE
, sex interaction, tau
