Peripheral Transport Proteins Were Associated with 4-Year Cognitive Decline in APOE ɛ4 Non-Carriers: A Longitudinal, Population-Based Study

Article type: Research Article

Authors: Gao, Ling^{a; 1} | Dang, Liangjun^{a; 1} | Wei, Shan^a | Hu, Ningwei^a | Gao, Fan^b | Peng, Wei^a | Shang, Suhang^a | Zhao, Yi^a | Chen, Chen^a | Guo, Xiaojuan^a | Huo, Kang^a | Wang, Jingyi^c | Wang, Jin^{a; *} | Qu, Qiumin^{a; d; *}

Affiliations: [a] Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China | [b] Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China | [c] Huyi Hospital of Traditional Chinese Medicine, Xi’an, China | [d] Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Correspondence: [*] Correspondence to: Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Rd, Xi’an 710061, China. Tel./Fax: +86 029 8532 4083. E-mails: drwangjin@163.com(J. Wang) and quqiumin@xjtufh.edu.cn (Q. Qu); ORCID: https://orcid.org/0000-0002-5634-6209 (Q. Qu), https://orcid.org/0000-0002-2703-0352 (J. Wang).

Note: [1] These authors contributed equally to this work.

Abstract: Background: Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) play major roles in peripheral clearance of amyloid-β (Aβ). Objective: To determine the relationship between baseline sLRP1/sRAGE and early cognitive decline in a longitudinal study and explore the possible effect of apolipoprotein E (APOE) on their association. Methods: Cognitively normal subjects were followed-up for 4 years. The baseline plasma levels of sLRP1 and sRAGE were measured using commercial ELISA kits. Global cognition was evaluated by Mini-Mental State Examination (MMSE), and cognitive decline was defined as a ≥2-point decrease of MMSE after 4 years. The association between baseline sLRP1/sRAGE and 4-year cognitive decline were analyzed using logistic regression analysis. Interaction analysis was performed to discover the potential effect of APOE genotype on the relationship. Results: 769 participants were included in the final analysis, with 122 subjects (15.86%) were cognitive decline. Baseline sLRP1/sRAGE levels were not associated with 4-year cognitive decline after multivariable adjustments in the total cohort. However, there was significant interaction effect between sRAGE and APOE genotype on cognitive decline (adjusted odds ratio [OR] = 2.09, 95% confidence interval [CI]: 1.13–3.86, p = 0.019). Lower levels of sRAGE were associated with increased risk of cognitive decline among APOE ɛ4 non-carriers (adjusted OR = 1.60, 95% CI: 1.04–2.48, p = 0.034). Conclusion: Individuals with lower levels of sRAGE had an increased risk of 4-year cognitive decline in APOE ɛ4 non-carriers, indicating that the association between sRAGE and cognitive decline might depend on the APOE genotype. However, the specific mechanisms need to be further elucidated.

Keywords: Alzheimer’s disease, apolipoprotein E, cognitive impairment, longitudinal study, plasma amyloid-β transporters

DOI: 10.3233/JAD-215228

Journal: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 801-812, 2022