Platelet-Derived Amyloid-β Protein Precursor as a Biomarker of Alzheimer’s Disease

Article type: Research Article

Authors: Wang, Qing^{a; 1} | Shi, Yachen^{a; 1} | Qi, Xinyang^{b; 1} | Qi, Lingyu^a | Chen, Xiang^a | Shi, Jingping^{b; *} | Xie, Chunming^{a; c; *} | Zhang, Zhijun^{a; c; d; *}

Affiliations: [a] Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, China | [b] Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China | [c] The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China | [d] The Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

Correspondence: [*] Correspondence to: Zhijun Zhang, Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, P.O. BOX 210009, No. 87 Dingjiaqiao Road, Nanjing, China. Tel.: +86 25 83262241; Fax: +86 25 832851; E-mail: janemengzhang@vip.163.com; Chunming Xie, Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, P.O. BOX 210009, No. 87 Dingjiaqiao Road, Nanjing, China. Tel.: +86 25 83262241; Fax: +86 25 832851; E-mail: chmxie@163.com; Jingping Shi, Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, P.O. BOX 210029, No. 264 Guangzhou Road, Nanjing, China. Tel.: +86 25 82296409; Fax: +86 25 82296409; E-mail: profshijp@163.com.

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

Abstract: Background:Platelet proteins may be associated with Alzheimer’s disease (AD) pathology. Objective:To investigate the relationship between platelet proteins and cerebrospinal fluid (CSF) biomarkers of AD and cognition in individuals with memory decline to identify effective screening methods for detecting the early stages of the disease. Methods:We classified 68 participants with subjective memory decline according to the ATN framework determined by CSF amyloid-β (A), CSF p-tau (T), and t-tau (N). All participants underwent Mini-Mental State Examination (MMSE) and platelet-related protein content testing. Results:Eighteen participants had normal AD biomarkers (NCs), 24 subjects had non-AD pathologic changes (non-AD), and 26 subjects fell within the Alzheimer’s continuum (AD). The platelet amyloid-β protein precursor (AβPP) ratio in the AD group was significantly lower than in the non-AD and NCs groups, and positively correlated with MMSE scores and CSF amyloid-β42 level, which could affect MMSE scores through CSF amyloid-β42. Levels of platelet phosphorylated-tau 231 and ser396/404 phosphorylated tau were elevated in both AD and non-AD compared to NCs. Additionally, the receiver operating characteristic analysis demonstrated that the platelet AβPP ratio was a sensitive identifier for differentiating the AD from NCs (AUC = 0.846) and non-AD (AUC = 0.768). And ser396/404 phosphorylated tau could distinguish AD from NCs. Conclusion:Our study was the first to find an association between platelet AβPP ratio and CSF biomarkers of AD, which contribute to the understanding of the peripheral changes in AD. These findings may help to discover potential feasible and effective screening tools for AD.

Keywords: Alzheimer’s disease, amyloid-β protein precursor ratio, ATN framework, cerebrospinal fluid, platelet

DOI: 10.3233/JAD-220122

Journal: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 589-599, 2022