Amyloid β neurotoxicity is IDO1–Kyn–AhR dependent and blocked by IDO1 inhibitor

Alzheimer’s disease (AD), the most common neurodegenerative disorder and a leading cause of dementia is characterized by progressive memory deficits, cognitive impairment and personality changes. The accumulation of extracellular amyloid beta (Aβ) plaques consisted by Aβ peptide and intracellular neurofibrillary tangles (NFTs) composed by misfolded hyperphosphorylated tau are main pathological hallmarks of AD, which ultimately lead to the dysfunction and loss of synapses and the eventual death of neuron. Neuroinflammation plays a causal role in AD pathogenesis. While the mechanism underlying neuroinflammation-induced AD pathology has not been fully elucidated, increasing evidence proposed that the kynurenine pathway (KP), a major route for l -tryptophan ( l -Trp) catabolism, plays an important role. 1