Vitamin B12 Levels in Alzheimer's Disease: Association with Clinical Features and Cytokine Production

Article type: Research Article

Authors: Politis, Antonis^a | Olgiati, Paolo^b | Malitas, Petros^c | Albani, Diego^d | Signorini, Alessandra^d | Polito, Letizia^d | De Mauro, Stefania^d | Zisaki, Aikaterini^e | Piperi, Christina^e | Stamouli, Evangelia^a | Mailis, Antonis^a | Batelli, Sara^d | Forloni, Gianluigi^d | De Ronchi, Diana^b | Kalofoutis, Anastasios^f | Liappas, Ioannis^g | Serretti, Alessandro^{b; *}

Affiliations: [a] Division of Geriatric Psychiatry Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece | [b] Institute of Psychiatry, University of Bologna, Bologna, Italy | [c] European Centre for the Quality of Life – E.C.Qua.L. Biomedical Research Foundation of the Academy of Athens, Greece | [d] Neuroscience Department, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy | [e] Department of Pharmacology, University of Athens Medical School, Athens, Greece | [f] Laboratory of Biological Chemistry, University of Athens Medical School, Athens, Greece | [g] Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece

Correspondence: [*] Corresponding author: Alessandro Serretti, MD, PhD, Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy. Tel.: +39 051 6584233; Fax: +39 051 521030; E-mail: [email protected].

Abstract: Alzheimer's disease (AD) has been associated with up-regulation of pro-inflammatory cytokines (e.g., specific gene variants for TNF-α; IL-6; IFN-γ) and low plasma levels of cyanocobalamin (vitamin B12). Our goal was to relate B12 levels to AD symptoms and to expression of pro-inflammatory cytokines. Clinical manifestations were investigated for a case series of fifty-five outpatients using the MMSE, Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia (CDDS). Plasma B12 levels were measured by radioligand binding assay. Basal and PMA-stimulated levels of IFN-γ, TNF-α, and IL-6 were measured by ELISPOT (PBMC culture supernatant). 47 patients were genotyped for APOE. Ten patients (18%) had their B12 levels below <250 pg/ml. They did not statistically differ from those 45 who had normal levels in most demographic and clinical features; their MMSE scores were lower (14.7 vs 19.6 p = 0.03) but not after adjustment for disease duration. A greater basal production of IL-6 was reported in patients who had low B12 levels compared to normal B12 subjects (1333 pg/ml vs 976 p < 0.01); this association was confirmed after controlling for age of onset and APOE genotype. In conclusion, low B12 level is associated with greater production of IL-6 in peripheral blood mononuclear cells. Further research is warranted to elucidate whether this neuroinflammatory effect of cobalamin is implicated in the pathophysiology of AD.

Keywords: Alzheimer's disease, APOE gene, cytokine, inflammatory response, vitamin B12

DOI: 10.3233/JAD-2010-1252

Journal: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 481-488, 2010