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

Tapan Kumar Sinha Roy,Aparajita Dhar,Sasanka Chakrabarti,Anindita Banerjee,Barun Mukhopadhyay,Atanu Biswas,Vineet Kumar Khemka,Debashree Roy

doi:10.14336/ad.2016.1017

Abstract

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.

Highlights

Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting the elderly population leading to progressive loss of memory and multiple cognitive functions [1]
Serum 25-hydroxyvitamin D was lower by nearly 50% in AD subjects with respect to controls (Fig. 1C)
When these parameters were compared between two sub groups of AD subjects, it was observed that serum IL 6 and TNF α levels were significantly higher (p

Summary

Introduction

Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting the elderly population leading to progressive loss of memory and multiple cognitive functions [1]. It has been established that elevated circulating pro-inflammatory cytokines through several well-defined mechanisms can increase the CNS cytokines which in turn can impact the mood, memory and cognition through alterations of synaptic properties, neurogenesis and neurotransmission at different brain regions as well as by changes in the amyloid beta peptide metabolism [34,35] It is likely from the collective evidence from experimental and epidemiological studies that a complex relationship exists among AD and depression through the operations of risk factors like the lower level of vitamin D and elevated levels of pro-inflammatory cytokines in peripheral circulation. In this context it is worthwhile to measure these serum parameters simultaneously in controls and AD patients with and without depression and to examine the statistical correlations among different variables

Methods

Results

Conclusion