Division of Geriatric Psychiatry Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece.
J Alzheimers Dis. 2010;19(2):481-8. doi: 10.3233/JAD-2010-1252.
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.
阿尔茨海默病（AD）与促炎细胞因子的上调有关（例如，TNF-α；IL-6；IFN-γ的特定基因变异）和低血浆氰钴胺素（维生素 B12）水平。我们的目标是将 B12 水平与 AD 症状和促炎细胞因子的表达相关联。使用 MMSE、神经精神病学问卷（NPI）和痴呆症的康奈尔抑郁量表（CDDS）对 55 例门诊患者的病例系列进行了临床表现调查。通过放射性配体结合测定法测量血浆 B12 水平。通过 ELISPOT（PBMC 培养上清液）测量 IFN-γ、TNF-α和 IL-6 的基础和 PMA 刺激水平。对 47 名患者进行 APOE 基因分型。有 10 名患者（18%）的 B12 水平低于<250 pg/ml。他们在大多数人口统计学和临床特征方面与那些 B12 水平正常的 45 名患者没有统计学差异；他们的 MMSE 评分较低（14.7 对 19.6 p=0.03），但在调整疾病持续时间后没有差异。与 B12 水平正常的患者相比，B12 水平较低的患者报告的 IL-6 基础产量更高（1333 pg/ml 对 976 p<0.01）；在控制发病年龄和 APOE 基因型后，这一关联得到了证实。总之，低 B12 水平与外周血单个核细胞中 IL-6 的产生增加有关。需要进一步的研究来阐明钴胺素的这种神经炎症作用是否与 AD 的病理生理学有关。
