Cerebrospinal Fluid Neurotransmitters, Cytokines, and Chemokines in Alzheimer’s and Lewy Body Diseases

Article type: Research Article

Authors: Lourenco, Mychael V.^a | Ribeiro, Felipe C.^a | Santos, Luis E.^a | Beckman, Danielle^a | Melo, Helen M.^a | Sudo, Felipe K.^b | Drummond, Cláudia^{b; c} | Assunção, Naima^{b; d} | Vanderborght, Bart^b | Tovar-Moll, Fernanda^{b; d} | De Felice, Fernanda G.^{a; e; f} | Mattos, Paulo^{b; d; g} | Ferreira, Sergio T.^{a; h; *}

Affiliations: [a] Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil | [b] D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil | [c] Department of Speech and Hearing Pathology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil | [d] Program in Morphological Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil | [e] Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Canada | [f] Department of Psychiatry, Queen’s University, Kingston, Canada | [g] Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil | [h] Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Correspondence: [*] Correspondence to: Sergio T. Ferreira, PhD, Institute of Biophysics Carlos Chagas Filho and Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, 21941-902, Rio de Janeiro, Brazil. Tel.: +55 21 39386579; E-mail: [email protected].

Abstract: Background:Alzheimer’s disease (AD) and Lewy body disease (LBD) are complex neurodegenerative disorders that have been associated with brain inflammation and impaired neurotransmission. Objective:We aimed to determine concentrations of multiple cytokines, chemokines, and neurotransmitters previously associated with brain inflammation and synapse function in cerebrospinal fluid (CSF) from AD and LBD patients. Methods:We examined a panel of 50 analytes comprising neurotransmitters, cytokines, chemokines, and hormones in CSF in a cohort of patients diagnosed with mild cognitive impairment (MCI), AD, LBD, or non-demented controls (NDC). Results:Among neurotransmitters, noradrenaline (NA) was increased in AD CSF, while homovanillic acid (HVA), a dopamine metabolite, was reduced in both AD and LBD CSF relative to NDC. Six cytokines/chemokines out of 30 investigated were reliably detected in CSF. CSF vascular endothelial growth factor (VEGF) was significantly reduced in LBD patients relative to NDC. Conclusions:CSF alterations in NA, HVA, and VEGF in AD and LBD may reflect pathogenic features of these disorders and provide tools for improved diagnosis. Future studies are warranted to replicate current findings in larger, multicenter cohorts.

Keywords: Alzheimer’s disease, cerebrospinal fluid, cytokines, homovanillic acid, inflammation, Lewy body disease, neurotransmitters, noradrenaline, vascular endothelial growth factor.

DOI: 10.3233/JAD-210147

Journal: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 1067-1074, 2021