Fig. 7

Possible mechanisms involved in the association between blood KP metabolites and Aβ in high NAL participants. Elevated blood kynurenine (KYN), anthranilic (AA), and 3-hydroxykynurenine (3-HK) concentrations in individuals with high neocortical amyloid-β load (NAL) [14] potentially have increased KYN, AA, and 3-HK concentrations in the brain, given that blood KYN, AA, and 3-HK concentrations account for ~ 60% of the brain pools of these metabolites, given their permeability to the blood-brain barrier [50]. This increase in the kynurenine pathway (KP) intermediate substrates could result in increased microglial activation which in turn can result in the secretion of inflammatory signalling molecules, which further trigger amyloid-β generation and immune responses, resulting in a vicious cycle. Further, immune responses such as interferon-γ activate indoleamine 2,3-dioxygenase result in increased tryptophan degradation and increased KP metabolites