Abnormal Tryptophan Metabolism in Alzheimer's Disease (ALZ): Label-free spectroscopy suggests an alternative theory of ALZ causation

The leading hypothesis regarding ALZ causation is that it is related to abnormal aggregation of beta-amyloid and tau in the brain. It is known that, under stress conditions, indoleamine 2,3-dioxygenase shifts tryptophan metabolism away from the serotonin pathway towards the kynurenine pathway. Using label-free spectroscopy of tryptophan, N-formyl-L-kynurenine, kynurenine and kynurenic acid in ALZ and age-matched controls, we showed that a reversal of normal tryptophan/kynurenine ratio occurs in heavily affected ALZ areas (hippocampus, Brodmann's Area 9), but not in minimally-affected areas such as Brodmann's Area 17. Since ALZ develops only in areas of the brain where excess kynurenines are produced, it is possible ALZ is caused by abnormal tryptophan metabolism rather than protein aggregation.