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

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.

Pterostilbene inhibits amyloid‐β‐induced neuroinflammation in a microglia cell line by inactivating the NLRP3/caspase‐1 inflammasome pathway

“…During AD, the activated microglia produces many kinds of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β. 15,18,19 Over secretion of pro-inflammatory cytokines contributes to the inflammatory response, leading to cell death 20,21 Thus inhibition of the pro-inflammatory cytokine production is helpful for the treatment of AD. The current study showed that Aβ 1−42 -induced secretion of IL-6, IL-1β, and TNF-α could be attenuated by pterostilbene.…”

Risk factors for Alzheimer’s disease

“…Nevertheless, Heyman et al [80] reported that a previous psychiatric morbidity was associated with AD while French et al [50] and Barclay et al [21] both suggested an association with depression. Subsequently, Bannerjee et al [20] investigated whether such associations were due to depression either being a risk factor or a co-morbidity of AD. It was concluded that the coexistence of the two conditions could reflect altered circulating levels of common metabolites such as cytokine K6, TNF-α, and serum 25 hydroxy-vitamin D. Increasing stress in early life has also been suggested as a risk factor for cognitive decline at a later age with evidence that stress may contribute to amyloid pathology in early stressed mice [82].…”

The Role of Immunosenescence in Neurodegenerative Diseases

“…These cells interact with microglia and A β plaques, considered as an inflammasome activator, producing cytokines and ROS, leading to neuronal loss and apoptosis [ 88 ]. To assess the immune system involvement, many authors evaluated the circulating levels of IL-6, TNF- α , and IFN γ production in AD patient serum/plasma [ 53 , 98 , 99 ], CSF (cerebrospinal fluid) [ 100 ], and derived peripheral blood mononuclear cells [ 101 ]. Circulating levels of proinflammatory cytokines are elevated and significantly associated with increased risk for AD cognitive decline.…”