Potential Biomarkers in Cerebrospinal Fluid and Plasma for Dementia

Article type: Research Article

Authors: He, Qiang^a | Wang, Wenjing^b | Xiong, Yang^c | Tao, Chuanyuan^a | Ma, Lu^a | You, Chao^{a; *}

Affiliations: [a] Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China | [b] Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu, China | [c] Department of Urology, West China Hospital, Sichuan University, Chengdu, China

Correspondence: [*] Correspondence to: Chao You, Department of Neurosurgery, West China Hospital, Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu 610041, Sichuan, China. E-mail: [email protected].

Abstract: Background:The identification of biomarkers for different dementias in plasma and cerebrospinal fluid (CSF) has made substantial progress. However, they are observational studies, and there remains a lack of research on dementias with low incidence rates. Objective:We performed a comprehensive Mendelian randomization to identify potential biomarkers for different dementia type. Methods:The summary-level datasets encompassed 734 plasma and 154 cerebrospinal fluid proteins sourced from recently published genome-wide association studies (GWAS). Summary statistics for different dementias, including any dementia (refering to any type of dementia symptoms, 218,792 samples), Alzheimer’s disease (AD, 63,926 samples), vascular dementia (212,389 samples), frontotemporal dementia (3,024 samples), dementia with Lewy bodies (DLB, 6,618 samples), and dementia in Parkinson’s disease (216,895 samples), were collected from large GWAS. The primary method is inverse variance weighting, with additional sensitivity analyses conducted to ensure the robustness of the findings. Results:The molecules released into CSF, namely APOE2 for any dementia, APOE2 and Siglec-3 for AD, APOE2 for vascular dementia, and APOE2 for DLB, might be potential biomarkers. CD33 for AD and SNCA for DLB in plasma could be promising biomarkers. Conclusions:This is the first study to integrate plasma and CSF proteins to identify potential biomarkers for different dementias.

Keywords: Alzheimer’s disease, association, biomarkers, cerebrospinal fluid, dementia, plasma, proteins

DOI: 10.3233/JAD-240260

Journal: Journal of Alzheimer's Disease, vol. 100, no. 2, pp. 603-611, 2024