15 Dec

PhD conferral Lieke Bakker

Supervisors: Dr. Sebastian Köhler, Prof. Dr. Frans R.J. Verhey

Co-supervisors: Dr. Inez H.G.B. Ramakers, Dr. Simone J.P.M Eussen

Keywords: Kynurenines, kynurenine pathway, cognitive functioning, dementia

"The Kynurenine Pathway and Cognitive Functioning A Transdiagnostic Approach"

This thesis investigated the relationship between kynurenines and cognitive function in healthy individuals and in different patient groups. Kynurenines are metabolites degraded from tryptophan, an essential amino acid, and can be found in various tissues, blood and cerebrospinal fluid. Some of these kynurenines may be neuroprotective whereas others appear to be neurotoxic. Results from previous studies suggest that kynurenines could play a role in neurodegenerative disorders such as Alzheimer's or Parkinson's disease, as well as stroke and even mood disorders. However, these studies were generally small and found inconsistent results.

The results from this thesis suggest that (1) several kynurenines are lower in individuals with Alzheimer's type dementia, (2) that kynurenines are associated with fewer Alzheimer’s disease related proteins in the brain and with neurodegeneration and (3) that kynurenines are associated with better brain functions. Taken together, these results provide strong evidence for the idea that higher levels of several kynurenines are beneficial for brain health. These discoveries are interesting, given the notion that kynurenine concentrations can be influenced by lifestyle and pharmacological interventions.

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