The Role of Amyloid-β, Tau, and α-Synuclein Proteins as Putative Blood Biomarkers in Patients with Cerebral Amyloid Angiopathy

Article type: Research Article

Authors: Piccarducci, Rebecca^a | Caselli, Maria Chiara^b | Zappelli, Elisa^a | Ulivi, Leonardo^b | Daniele, Simona^a | Siciliano, Gabriele^b | Ceravolo, Roberto^b | Mancuso, Michelangelo^b | Baldacci, Filippo^{b; *} | Martini, Claudia^{a; *}

Affiliations: [a] Department of Pharmacy, University of Pisa, Pisa, Italy | [b] Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Correspondence: [*] Correspondence to: Claudia Martini, Department of Pharmacy, University of Pisa, 56126, Pisa, Italy. Tel.: +39 050 2219522; E-mail: claudia.martini@unipi.it. and Filippo Baldacci, Department of Clinical and Experimental Medicine, University of Pisa, 56126, Pisa, Italy. Tel.: +39 050 993046; E-mail: filippo.baldacci@unipi.it.

Abstract: Background:Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by the deposition of amyloid-β protein (Aβ) within brain blood vessels that develops in elderly people and Alzheimer’s disease (AD) patients. Therefore, the investigation of biomarkers able to differentiate CAA patients from AD patients and healthy controls (HC) is of great interest, in particular in peripheral fluids. Objective:The current study aimed to detect the neurodegenerative disease (ND)-related protein (i.e., Aβ1-40, Aβ1-42, tau, and α-synuclein) levels in both red blood cells (RBCs) and plasma of CAA patients and HC, evaluating their role as putative peripheral biomarkers for CAA. Methods:For this purpose, the proteins’ concentration was quantified in RBCs and plasma by homemade immunoenzymatic assays in an exploratory cohort of 20 CAA patients and 20 HC. Results:The results highlighted a significant increase of Aβ1-40 and α-synuclein concentrations in both RBCs and plasma of CAA patients, while higher Aβ1-42 and t-tau levels were detected only in RBCs of CAA individuals compared to HC. Moreover, Aβ1-42/Aβ1-40 ratio increased in RBCs and decreased in plasma of CAA patients. The role of these proteins as candidate peripheral biomarkers easily measurable with a blood sample in CAA needs to be confirmed in larger studies. Conclusion:In conclusion, we provide evidence concerning the possible use of blood biomarkers for contributing to CAA diagnosis and differentiation from other NDs.

Keywords: α-synuclein, amyloid-β, biomarkers, cerebral amyloid angiopathy, plasma, red blood cells, tau

DOI: 10.3233/JAD-220216

Journal: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 1039-1049, 2022