The role of inflammatory processes in the development of depression and Alzheimer’s disease
Bruin, I.N. de
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Studies have suggested a link between experiencing episodes of depression and the subsequent development of dementia later in life. Evidence of this link consists of neuroanatomical similarities, including a decrease in hippocampal volume, as well as the epidemiological finding that the risk of dementia increases with 13-14% for every depressive episode. However, information on the cellular and molecular mechanism underlying the link between these disorders is limited. Inflammation is known to play an important role in both diseases, and is suggested as a candidate system involved in the link between both diseases. More specifically, it was recently suggested that the enzyme indoleamine 2,3-dioxygenose (IDO) may be an important player in the association between depression and dementia. IDO is the rate-limiting enzyme in the kynurenine pathway for tryptophan metabolism and is activated by pro-inflammatory cytokines. The aim of this thesis is to review evidence for a causal the link between both diseases and to test the plausibility of inflammation, and more specifically IDO, as a mechanistic factor. There is both qualitative and quantitative evidence that supports the hypothesis that IDO contributes to the symptoms of major depression as well as to the cognitive symptoms of Alzheimer’s disease. IDO exhibits this detrimental effect in close collaboration with the immune system and the hypothalamus-pituitary-adrenal (HPA)-axis. Therapeutic options based on alleviating IDO levels are suggested, but not proven irrefutably yet.