Altered Expression Profile of Phosphatidylinositols in Erythrocytes of Alzheimer’s Disease and Amnestic Mild Cognitive Impairment Patients

Article type: Research Article

Authors: Chen, Yanxing^{a; 1} | Lin, Caixiu^{a; b; 1} | Guo, Zhangyu^{a; c} | Zhao, Shuai^a | Zhu, Yueli^a | Huang, Fude^d | Shui, Guanghou^e | Lam, Sin Man^{e; f} | Pu, Jiali^a | Yan, Yaping^a | Liu, Zhirong^a | Zhang, Baorong^{a; *}

Affiliations: [a] Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China | [b] Department of Neurology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China | [c] Department of Pathology, Weifang Medical University, Weifang, China | [d] Shanghai Advanced Research Institute, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China | [e] StateKey Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China | [f] LipidALL Technologies Company Limited, Changzhou, Jiangsu Province, China

Correspondence: [*] Correspondence to: Baorong Zhang, Department∥of Neurology, the Second Affiliated Hospital, Zhejiang∥University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China. Tel.: +86 571 87784752; Fax: 86 571 87784750; E-mail: [email protected].

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

Abstract: Background:Studies have demonstrated that the levels of phospholipids, including phosphatidylinositols (PIs), were decreased in Alzheimer’s disease (AD) brain, presenting as a potential biomarker for AD. The plasma phospholipids levels have also been discovered to predict the conversion of cognitively normal elderly adults to amnestic mild cognitive impairment (aMCI) or demented patients. Objective:To investigate the expression profile of PIs in erythrocytes of AD and aMCI patients, which would serve as a blood-based method to distinguish AD and aMCI patients from normal controls (NC). Methods:In this study, we used anion-exchange high-performance liquid chromatography to analyze PIs alterations in erythrocytes from a total of 86 prospectively recruited subjects (including 24 NC, 21 aMCI patients, and 41 AD patients). Results:We found that the levels of PI40 : 4, PI3/5P, and PI(3,4)P2 in aMCI patients, and the levels of PI4P, PI(3,4)P2, and PI3/5P in AD patients were significantly decreased compared to NC. The changed expression profile of PIs could effectively discriminate AD and aMCI patients from NC (AUC = 0.964, 0.938, respectively). Conclusion:The altered expression profile of erythrocytes PIs might be a potential blood-based biomarker for AD and aMCI. This alteration of PIs probably reflected the impaired deformability and oxygen-carrying capacity of erythrocytes in AD and aMCI patients.

Keywords: Alzheimer’s disease, biomarker, erythrocytes, mild cognitive impairment, phosphatidylinositols

DOI: 10.3233/JAD-190926

Journal: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 811-818, 2020