Role of Pro-Inflammatory Cytokines and Vitamin D in Probable Alzheimer's Disease with Depression

Symptoms of depression are present in a significant proportion of Alzheimer's disease (AD) patients. While epidemiological studies have shown a strong association between depression and AD, it has not been established whether depression is a risk factor or merely a co-morbidity of AD. It is also uncertain if depression affects the pathogenesis of AD. In this paper, we address these questions by measuring the serum levels of two common metabolic risk factors of AD and depression, inflammatory cytokines (IL 6 and TNF alpha) and serum 25-hydroxyvitamin D, in a case-control study. We measured the serum levels of IL 6, TNF a and 25-hydroxyvitamin D in age-matched healthy controls (n= 60) and in AD patients without depression (n=26) or AD patients with depression (n=34), and statistically analyzed the changes in these parameters among different groups under this study. Our results show that in AD there is a significant increase in IL 6 and TNF a and a marked decrease in 25-hydroxyvitamin D in the peripheral circulation compared to age-matched healthy controls. Furthermore, AD patients with depression have even significantly higher levels of IL 6 or TNF a and a lower level of 25-hydroxyvitamin D in circulation than in AD patients without depression. We also found a strong statistical correlation between the disease severity and the serum levels of IL 6, TNF a and 25-hydroxyvitamin D in AD patients with depression. These results suggest that altered circulating levels of common metabolic risk factors lead to the co-existence of depression with AD in many patients, and when they co-exist, the depression presumably affects the severity of AD presentations through more aggravated changes in these risk factors.