Immune activation in patients with Alzheimer's disease is associated with high serum phenylalanine concentrations

Background: Immune activation and inflammation represent critical factors in the pathogenesis of Alzheimer's disease (AD) and are associated with increased blood concentrations of markers like neopterin and the kynurenine to tryptophan ratio (Kyn/Trp). In chronic inflammatory conditions, also increased serum phenylalanine concentrations and phenylalanine to tyrosine ratios (Phe/Tyr) were reported and could relate to neuropsychiatric symptoms. Objective: To examine serum phenylalanine and tyrosine concentrations in patients with AD and to compare results to neopterin and Kyn/Trp levels. Materials and methods: Serum was collected from 43 patients with AD and concentrations of phenylalanine and tyrosine as well as neopterin, tryptophan and kynurenine were measured and Phe/Tyr and Kyn/Trp were calculated. Results: A subgroup of AD patients presented with increased phenylalanine and Phe/Tyr concentrations, phenylalanine levels correlated with neopterin (rs = 0329), kynurenine (rs = 0.352) and Kyn/Trp levels (rs = 0288; all p < 0.05). There was no significant relationship between phenylalanine metabolism and cognitive ability test scores mini-mental state examination and clock drawing test. Conclusions: Higher serum phenylalanine concentrations related to immune activation are detectable in a subgroup of AD patients. The impaired conversion of phenylalanine may affect not only the production of tyrosine but also the biosynthesis of the neurotransmitters dopamine, norepinephrine and epinephrine. Further studies are justified in patients with AD to investigate a possible role of phenylalanine biochemistry in the development of neurovegetative and behavioral abnormalities. (C) 2013 Elsevier B.V. All rights reserved.