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

J Alzheimers Dis. 2010;19(2):481-8. doi: 10.3233/JAD-2010-1252.

Abstract

Alzheimer's disease (AD) has been associated with up-regulation of pro-inflammatory cytokines (e.g., specific gene variants for TNF-alpha; IL-6; IFN-gamma) 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-gamma, TNF-alpha, 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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Analysis of Variance
  • Apolipoprotein E4 / genetics
  • Cytokines / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Male
  • Mental Status Schedule
  • Neuropsychological Tests
  • Radioimmunoassay / methods
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / pharmacology
  • Up-Regulation / physiology*
  • Vitamin B 12 / blood*

Substances

  • Apolipoprotein E4
  • Cytokines
  • 4-O-methyl-12-O-tetradecanoylphorbol 13-acetate
  • Tetradecanoylphorbol Acetate
  • Vitamin B 12