Role of Pro-Inflammatory Cytokines and Vitamin D in Probable Alzheimer's Disease with Depression
Banerjee Anindita1,2, Khemka Vineet Kumar1,2, Roy Debashree2, Dhar Aparajita2, Sinha Roy Tapan Kumar2, Biswas Atanu3, Mukhopadhyay Barun4, Chakrabarti Sasanka1,*
1Department of Biochemistry, ICARE Institute of Medical Sciences and Research, Haldia, India. 2Department of Biochemistry, Institute of Post Graduate Medical Education and Research, Kolkata, India. 3Department of Neurology, Bangur Institute of Neurosciences, Kolkata, India. 4Biological Anthropology Unit, Indian Statistical Institute, Kolkata, India.
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 α 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 α 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 α 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 α 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.
Table 1 Demographic and biochemical profile of the subjects
Figure 1. Serum levels of IL 6, TNF α and 25-hydroxyvitamin D (25 OH vitamin D) in AD subjects
Values are expressed as the means ± SD for the number of cases in each group of subjects. Statistically significant, p<0.0001 AD vs. Control.
Figure 2. Serum levels of IL 6, TNF α, 25-hydroxyvitamin D (25OH vitamin D) and MMSE in AD subjects with depression (AD with dep) and without depression (AD without dep)
Box and Whisker plots represent median, upper median, lower median, and minimum to maximum range of serum IL 6 (A), TNF α (B) and 25-hydroxyvitamin D (C) while Bar diagram represents mean MMSE (D) among AD subjects with and without depression. Values expressed as the means ± SD are: IL 6 (pg/ml) 10.47±4.18 (AD with depression), 4.56±1.20 (AD without depression); TNFα (pg/ml) 16.84±3.88 (AD with depression), 13.48±2.92 (AD without depression); 25-hydroxyvitamin D (ng/ml) 10.22 ± 3.22 (AD with depression), 15.61 ± 4.64 (AD without depression); MMSE 10.9±4.38 (AD with depression), 19.15±1.46 (AD without depression). Statistically significant difference, p < 0.001, AD subjects with depression versus AD subjects without depression.
Figure 3. Correlation between MMSE scores and serum levels of 25-hydroxyviamin D (25 OH vitamin D) or IL 6 orTNF α in AD with or without depression. XY scatter plots are shown between MMSE scores and serum levels of 25-hydroxyvitamin D (A) or IL 6 (B) or TNF α (C) in AD subjects with depression or serum levels of 25-hydroxyvitamin D (D) or IL 6 (E) or TNF α (F) in AD subjects without depression. The degree and nature of correlation between the MMSE score and the serum parameter in AD patients is given by the value of r (correlation coefficient) as explained in the methods. A value of p < 0.05 was considered as statistically significant.
Figure 4. XY scatter plots between serum levels of 25-hydroxyvitamin D (25 OH Vitamin D) and IL 6 or TNF α in AD with or without depression. The degree and nature of correlation between the MMSE score and the serum parameter in AD patients is given by the value of r (correlation coefficient) as explained in the methods. A value of p < 0.05 was considered as statistically significant.
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