CCL23: A Chemokine Associated with Progression from Mild Cognitive Impairment to Alzheimer’s Disease

Article type: Research Article

Authors: Faura, Júlia^a | Bustamante, Alejandro^{a; b} | Penalba, Anna^a | Giralt, Dolors^a | Simats, Alba^a | Martínez-Sáez, Elena^c | Alcolea, Daniel^{d; e} | Fortea, Juan^{d; e} | Lleó, Alberto^{d; e} | Teunissen, Charlotte E.^f | van der Flier, Wiesje M.^{g; h} | Ibañez, Laura^{i; j} | Harari, Oscar^{i; j} | Cruchaga, Carlos^{i; j} | Hernández-Guillamón, Mar^a | Delgado, Pilar^a | Montaner, Joan^{a; *}

Affiliations: [a] Neurovascular Research Laboratory. Vall d’Hebron Institut de Recerca (VHIR) – Universitat Autònoma de Barcelona, Barcelona, Spain | [b] Neurology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain | [c] Neuropathology Unit, Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain | [d] Sant Pau Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain | [e] Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Spain | [f] Department of Clinical Chemistry, Neurochemistry Laboratory and Biobank, VU University Medical Center, Amsterdam, The Netherlands | [g] Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands | [h] Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands | [i] Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA | [j] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA

Correspondence: [*] Correspondence to: Joan Montaner, Neurovascular Research Laboratory, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119-129, 08035 Barcelona, Spain. Tel.: +34 934894029; Fax: +34 934894015; E-mail: joan.montaner@vhir.org.

Abstract: CCL23 is a chemokine implicated in inflammation and host defense responses. It has been recently associated with acquired brain damage and stroke outcomes. In this study, we reported the role of CCL23 in Alzheimer’s disease (AD). We evaluated the levels of CCL23 in 659 individuals: cognitively normal, mild cognitive impaired (MCI), and AD patients. Two cross-sectional (study 1, n = 53; study 2, n = 200) and two longitudinal (study 3, n = 74; study 4, n = 332) studies were analyzed separately. CCL23 levels in the blood and/or cerebrospinal fluid (CSF) of each study were measured by immunoassays. Globally, our results suggest a predictive role of CCL23 protein levels both in the plasma in study 3 (hazard ratio (HR) = 2.5 (confidence interval (CI) 95% : 1.2–5.3), p = 0.02) and in the CSF in study 4 (HR = 3.05 (CI 95% : 1.02–5), p = 0.04) in cases of MCI that progress to AD. Moreover, we observed that the APOE ɛ4 allele was associated with higher levels of CCL23 in study 2 (470.33 pg/mL (interquartile range (IQR): 303.33–597.76) versus 377.94 pg/mL (IQR: 267.16–529.19), p = 0.01) (APOE genotypes were available in studies 2 and 4). Together, these findings support the role of CCL23 in neuroinflammation in the early stages of AD, suggesting that CCL23 might be a candidate blood biomarker for MCI to AD progression.

Keywords: Alzheimer’s disease, biomarkers, chemokines, cognitive dysfunction, early diagnosis

DOI: 10.3233/JAD-190753

Journal: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1585-1595, 2020