Free amino acid and dipeptide changes in the body fluids from Alzheimer’s disease subjects

Abstract

Our aim was to determine changes in free amino acid (FAA) and dipeptide (DP) concentrations in probable Alzheimer's disease (pAD) subjects compared with control (CT) subjects using liquid chromatography and electrospray ionization tandem mass spectrometry (LCMS2). We recruited gender- and age-matched study participants based on neurological and neuropsychological assessments. We measured FAAs and DPs in cerebrospinal fluid (CSF), plasma and urine using LCMS2 with selected reaction monitoring (SRM). Imidazole-containing FAAs (histidine, methyl-histidine), catecholamines (L-DOPA and dopamine), citrulline, ornithine, glycine and antioxidant DPs (carnosine and anserine) accounted for the major changes between CT and pAD. Carnosine levels were significantly lower in pAD (328.4 +/- 91.31 nmol/dl) than in CT plasma (654.23 +/- 100.61 nmol/dl). In contrast, L-DOPA levels were higher in pAD (1400.84 +/- 253.68) than CT (513.10 +/- 121.61 nmol/dl) plasma. These data underscore the importance of FAA and DP metabolism in the pathogenesis of AD. Since our data show changes in antioxidants, neurotransmitters and their precursors, or FAA associated with urea metabolism in pAD compared with CT, we propose that manipulation of these metabolic pathways may be important in preventing AD progression.

Platelet serotonin concentration and monoamine oxidase type B activity in female patients in early, middle and late phase of Alzheimer's disease

“…The literature data on tryptophan concentrations in body fluids and brain of patients with AD are inconsistent. The majority of studies have found low tryptophan concentrations in serum (Widner et al 2000), plasma (Fekkes et al 1998) and CSF (Tohgi et al 1992) while other studies showed no alterations in tryptophan concentrations in plasma (Fonteh et al 2007) and brain (Storga et al 1996) in patients with AD. Low plasma tryptophan concentration might be also a consequence of the enhanced tryptophan degradation via the kynuramine pathway (Widner et al 2000), since a dysregulation of both serotonergic and kynuramine pathways of tryptophan metabolism have been associated with pathophysiology of AD (Ruddick et al 2006).…”

P2‐452: Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg‐AD mice

“…However, one possible limitation in employing carnosine as an anti-AD drug is that brain carnosine is rapidly inactivated by the activity of three different isoforms of the carnosine degrading enzyme, carnosinase. Increased carnosinase activity has in fact been found in AD patients as well as in aging individuals [27,28] and decreased plasmatic levels of carnosine have been reported in AD patients [29].…”

Metabolomics in the Study of Alzheimer's Disease

“…Interestingly compared to control subjects near 30% and 60% of the metabolic pathways altered in the CSF of MCI and AD patients respectively, were also affected in plasma samples from the same individuals showing certain correlation between biofluids [123]. Amino acid and dipeptide content correlation between CSF and plasma was also accomplished by Fonteh et al including also urine in that case [98]. CSF, plasma and urine from 8 AD patients and 8 control subjects were submitted to metabolite extraction.…”

“…Most of them are based on the analysis of CSF, blood or post-mortem brain tissue samples, although in a lesser extent, urine has been also examined in the search of AD biomarkers [89,98].…”

“…3 [98] metabolic variations due to AD were very different among the three biofluids. Altered metabolites due to AD pathology were identified and related to different biochemical processes such as neurotransmission (L-Dopa and dopamine), urea cycle/detoxification or NO formation (arginine, citrulline, ornithine), inhibitory processes (glycine) and antioxidation (carnosine) [98].…”