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

摘要

The leading hypothesis regarding ALZ causation is that it is related to abnormal aggregation of β-amyloid and tau inthe brain. It is known that, under stress conditions, indoleamine 2,3-dioxygenase shifts tryptophan metabolism awayfrom 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 normaltryptophan/kynurenine ratio occurs in heavily affected ALZ areas (hippocampus, Brodmann’s Area 9), but not inminimally-affected areas such as Brodmann’s Area 17. Since ALZ develops only in areas of the brain where excesskynurenines are produced, it is possible ALZ is caused by abnormal tryptophan metabolism rather than proteinaggregation.