Vitamin B12 levels in Alzheimer's disease: association with clinical features and cytokine production.
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.
Politis
Antonis
A
Division of Geriatric Psychiatry Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece.
Olgiati
Paolo
P
Malitas
Petros
P
Albani
Diego
D
Signorini
Alessandra
A
Polito
Letizia
L
De Mauro
Stefania
S
Zisaki
Aikaterini
A
Piperi
Christina
C
Stamouli
Evangelia
E
Mailis
Antonis
A
Batelli
Sara
S
Forloni
Gianluigi
G
De Ronchi
Diana
D
Kalofoutis
Anastasios
A
Liappas
Ioannis
I
Serretti
Alessandro
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D011863:Radioimmunoassay / Q000379:methods; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology*; D014805:Vitamin B 12 / Q000097:blood*
D053327:Apolipoprotein E4; D016207:Cytokines; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D013755:Tetradecanoylphorbol Acetate; D014805:Vitamin B 12