Vitamin D in Alzheimer’s Disease: Low Levels in Cerebrospinal Fluid Despite Normal Amounts in Serum

Article type: Research Article

Authors: Soares, Jelena Zugic^{a; b; i; *} | Valeur, Jørgenⁱ | Šaltytė Benth, Jūratė^{c; d} | Knapskog, Anne-Brita^e | Selbæk, Geir^{b; e; f} | Arefi, Golchin^h | Gilfillan, Gregor D.^h | Tollisen, Anitaⁱ | Bogdanovic, Nenad^{e; g} | 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] Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway | [d] Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway | [e] Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway | [f] Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway | [g] Department for Neurobiology, Caring Science and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden | [h] Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway | [i] Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway

Correspondence: [*] Correspondence to: Jelena Z. Soares, Lovisenberggata 17, 0456 Oslo, Norway. Tel.: +47 97146111; E-mail: jelenazugichotmail.com.

Abstract: Background:Vitamin D insufficiency has been suggested as a dementia risk factor. Objective:In this cross-sectional, explorative study we investigated whether levels of vitamin D in cerebrospinal fluid (CSF) are lower in patients with positive biomarkers of Alzheimer’s disease (AD) compared to cognitively healthy controls and whether polymorphisms of the vitamin D receptor (VDR) gene, FokI, BsmI, ApaI, and TaqI, are associated with levels of vitamin D in CSF and cognition. Methods:We included 100 patients≥65 years assessed for cognitive impairment and 76 cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D) in both serum and CSF, and VDR polymorphisms were analyzed. Results:The mean level of 25(OH)D in serum was 78.6 (SD 28.9) nmol/l. While serum levels of 25(OH)D were not significantly different between the groups, CSF levels of 25(OH)D were significantly lower in patients with positive AD core biomarkers (p = 0.001) compared to patients without such biomarkers. Individuals with the BsmI major homozygote genotype had significantly lower results on a 10-word delayed recall test (p = 0.044) and verbal fluency test (p = 0.013), and individuals with the TaqI major homozygote genotype had significantly lower results on a verbal fluency test (p = 0.030) compared to individuals with the corresponding minor homozygote genotype. Conclusion:Patients with positive AD core biomarkers have low CSF levels of 25(OH)D, despite sufficient serum levels. CSF levels of 25(OH)D do not seem to be affected by any of the four VDR gene polymorphisms. TaqI and BsmI major homozygote genotypes might be at increased risk for development of cognitive decline.

Keywords: Alzheimer’s disease, blood-brain barrier, cerebrospinal fluid, cognitive function, dementia, polymorphism, single nucleotide, vitamin D, vitamin D3 receptor

DOI: 10.3233/JAD-215536

Journal: Journal of Alzheimer's Disease, vol. 86, no. 3, pp. 1301-1314, 2022