Cognitive Decline and Alzheimer’s Disease in Old Age: A Sex-Specific Cytokinome Signature

Article type: Research Article

Authors: Boccardi, Virginia^{a; *} | Paolacci, Lucia^a | Remondini, Daniel^b | Giampieri, Enrico^b | Poli, Giulia^c | Curti, Nico^b | Cecchetti, Roberta^a | Villa, Alfredo^d | Ruggiero, Carmelinda^a | Brancorsini, Stefano^c | Mecocci, Patrizia^a

Affiliations: [a] Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy | [b] Department of Physics and Astronomy, University of Bologna, and INFN Bologna, Bologna, Italy | [c] Department of Experimental Medicine, Section of Terni, University of Perugia, Perugia, Italy | [d] Department of Clinical Pathology, S.M. della Misericordia Hospital, Perugia, Italy

Correspondence: [*] Correspondence to: Virginia Boccardi, MD, PhD, Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, Italy. Tel.: +39 0755783524; E-mail: virginia.boccardi@unipg.it.

Abstract: Background:Elevated peripheral levels of different cytokines and chemokines in subjects with Alzheimer’s disease (AD), as compared with healthy controls (HC), have emphasized the role of inflammation in such a disease. Considering the cross-talking between the central nervous system and the periphery, the inflammatory analytes may provide utility as biomarkers to identify AD at earlier stages. Objective:Using an advanced statistical approach, we can discriminate the interactive network of cytokines/chemokines and propose a useful tool to follow the progression and evolution of AD, also in light of sex differences. Methods:A cohort of 289 old-age subjects was screened for cytokine and chemokine profiling, measured in plasma, after a thorough clinical and neuropsychological evaluation. A custom algorithm based on Fisher linear discriminant analysis was applied to ascertain a classification signature able to discriminate HC from mild cognitive impairment (MCI) and AD. Results:We observed that a joint expression of three proteins (a “signature” composed by IFN-α2, IL-1α, TNFα) can discriminate HC from AD with an accuracy of 65.24%. Using this signature on MCI samples, 84.93% of them were classified as “non-HC”. Stratifying MCI samples by sex, we observed that 87.23% of women were classified as “non-HC”, and only 57.69% of males. Indeed, in a scatter plot of IFN-α2 and IL-1α, the HC group was better separated from MCI and AD in women as compared with men. Conclusion:These findings suggest that AD is accompanied by a peripheral inflammatory response that can already be present in MCI subjects, thus providing a mean for detecting this at-risk status and allow an anticipated intervention.

Keywords: Cytokines, dementia, inflammation, markers, sex

DOI: 10.3233/JAD-190480

Journal: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 911-918, 2019