The role of inflammatory processes in the development of depression and Alzheimer’s disease
Summary
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.