Associations Between Intrathecal Levels of Vitamin D, Cytokines, and Core Biomarkers of Alzheimer’s Disease: A Cross-Sectional Study

Article type: Research Article

Authors: Soares, Jelena Zugic^{a; b; c; *} | Valeur, Jørgen^c | Šaltytė Benth, Jūratė^{d; e} | Knapskog, Anne-Brita^f | Selbæk, Geir^{b; f; g} | Bogdanovic, Nenad^{f; h} | Pettersen, Renate^a

Affiliations: [a] Medical Department, Section of Geriatrics, Lovisenberg Diaconal Hospital, Oslo, Norway | [b] Faculty of Medicine, University of Oslo, Oslo, Norway | [c] Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway | [d] Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway | [e] Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway | [f] Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway | [g] Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway | [h] Department for Neurobiology, Caring Science and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden

Correspondence: [*] Correspondence to: Jelena Zugic Soares, Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital. Postboks 4970-Nydalen. 0440 Oslo, Norway. Tel.: +47 97146111; E-mail: [email protected].

Abstract: Background:Several studies have examined association between vitamin D levels in serum and cognition, but little is known of vitamin D levels in cerebrospinal fluid (CSF) and association with Alzheimer’s disease (AD). Objective:In this cross-sectional, explorative study we investigated possible associations of vitamin D in CSF with biomarkers for AD, amyloid-β, tau protein/phosphorylated tau protein in CSF, and with the cytokines IL-6, IL-8, and TNF-α in CSF in patients with cognitive impairment and cognitively healthy controls. Methods:We included 100 outpatients ≥65 years referred for assessment of cognitive impairment and 76 age- and sex-matched cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D), amyloid-β, tau protein and phosphorylated tau protein, as well as IL-6, IL-8, and TNF-α, were analyzed in CSF in both groups. Results:Higher levels of 25(OH)D in CSF in all groups together were associated with lower levels of tau protein (p = 0.01) and phosphorylated tau protein (p = 0.005). We found no association between 25(OH)D levels in CSF and pathological levels of amyloid-β in CSF nor levels of IL-6 or TNF-α in CSF. Higher levels of 25(OH)D in CSF were associated with higher levels of IL-8 in CSF (p = 0.002). However, vitamin D explained only 6% of variance in IL-8. There was no significant difference between the patient groups and the control group regarding the association between 25(OH)D in CSF and any of the three cytokines in CSF. Conclusion:Participants with higher CSF levels of 25(OH)D exhibited reduced CSF levels of tau protein and phosphorylated tau protein.

Keywords: Alzheimer’s disease, blood-brain barrier, cerebrospinal fluid, cognitive function, cytokines, dementia, tau protein, vitamin D

DOI: 10.3233/JAD-220407

Journal: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 825-834, 2022