Relationship Between Peripheral Transport Proteins and Plasma Amyloid-β in Patients with Alzheimer’s Disease Were Different from Cognitively Normal Controls: A Propensity Score Matching Analysis

Article type: Research Article

Authors: Gao, Ling^{a; 1} | Wang, Jin^{a; 1} | Jiang, Yu^a | Wei, Shan^a | Shang, Suhang^a | Chen, Chen^a | Dang, Liangjun^a | Huo, Kang^a | Deng, Meiying^a | Wang, Jingyi^b | Qu, Qiumin^{a; *}

Affiliations: [a] Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China | [b] Huxian Hospital of Traditional Chinese Medicine, Xi’an, China

Correspondence: [*] Correspondence to: Qiumin Qu, Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Rd, Xi’an 710061, China. Tel./Fax: +86 29 8532 4083; E-mail: [email protected].

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

Abstract: Background:Transport proteins, soluble LRP1 (sLRP1) and soluble RAGE (sRAGE), play a pivotal role in the peripheral clearance of plasma amyloid-β (Aβ). However, their relationship is seldom discussed, especially in Alzheimer’s disease (AD). Objective:To explore whether their relationship in patients with AD varied from those in cognitively normal (CN) controls. Methods:We initially recruited 70 patients with AD and 725 CN controls, then applied propensity score matching (PSM) analysis to balance the differences between two groups. Plasma levels of sLRP1, sRAGE, and Aβ were measured using commercial ELISA kits and log transformed when skewed distributed. The relationship between sLRP1/sRAGE and plasma Aβ were analyzed using Pearson’s correlation analysis followed by multiple linear regression separately in the original population and matched participants. Results:After PSM, 70 patients with AD and 140 matched controls were included for further analysis. Log sLRP1 was positively correlated with plasma Aβ40 in matched CN controls (r = 0.222, p = 0.008) but not in patients with AD (r = 0.137, p = 0.260). After multivariable adjustment, Log sLRP1 remained significantly associated with plasma Aβ40 in the CN group (β= 7.347, p = 0.014) but not in the AD group (β= 10.409, p = 0.105). In contrast, Log sLRP1 was not correlated with plasma Aβ42 in patients with AD or CN controls, and Log sRAGE was consistently not associated with plasma Aβ40 or Aβ42 in either group. Conclusion:The significant correlation between sLRP1 and plasma Aβ40 present in CN controls was not found in patients with AD, suggesting that their relationship was different in AD. However, the specific mechanisms and its influence on cerebral amyloid burden require further validation.

Keywords: Alzheimer’s disease, plasma amyloid-β, propensity score matching, soluble low-density lipoprotein receptor-related protein-1, soluble receptor of advanced glycation end products

DOI: 10.3233/JAD-191320

Journal: Journal of Alzheimer's Disease, vol. 78, no. 2, pp. 699-709, 2020