Vitamin B12 levels in Alzheimer's disease: Association with clinical features and cytokine production

Antonis Politis, Paolo Olgiati, Petros Malitas, Diego Albani, Alessandra Signorini, Letizia Polito, Stefania De Mauro, Aikaterini Zisaki, Christina Piperi, Evangelia Stamouli, Antonis Mailis, Sara Batelli, Gianluigi Forloni, Diana De Ronchi, Anastasios Kalofoutis, Ioannis Liappas, Alessandro Serretti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)481-488
Number of pages8
JournalJournal of Alzheimer's Disease
Volume19
Issue number2
DOIs
Publication statusPublished - 2010

Keywords

  • Alzheimer's disease
  • APOE gene
  • Cytokine
  • Inflammatory response
  • Vitamin B12

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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    Politis, A., Olgiati, P., Malitas, P., Albani, D., Signorini, A., Polito, L., De Mauro, S., Zisaki, A., Piperi, C., Stamouli, E., Mailis, A., Batelli, S., Forloni, G., De Ronchi, D., Kalofoutis, A., Liappas, I., & Serretti, A. (2010). Vitamin B12 levels in Alzheimer's disease: Association with clinical features and cytokine production. Journal of Alzheimer's Disease, 19(2), 481-488. https://doi.org/10.3233/JAD-2010-1252