Low plasma tryptophan is associated with olfactory function in healthy elderly community dwellers in Japan

Adachi, Yusuke; Shimodaira, Yoshiki; Nakamura, Hidehiro; Imaizumi, Akira; Mori, Maiko; Kobayashi, Yôko; Noguchi, Yasushi; Seki, Asuka; Okabe, Yuki; Miyake, Yuko; Ono, Kaori; Kumagai, Shinya

doi:10.1186/s12877-017-0639-5

Cited by 8 publications

(8 citation statements)

References 30 publications

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“…Our results suggest an overactivation of the KP during aging since we found a negative correlation between age and Trp levels and a positive influence of age on Kyn/Trp, KYNA/Trp, and 3-HK/Trp ratios; which is supported by the fact that the serum Kyn/Trp ratio is a measure of the beginning of KP activity [33, 34]. These data are consistent with previous studies in which low plasma, serum, and CSF Trp levels and high values of the Kyn/Trp ratio were also observed in elderly people [22, 23, 33, 35–39]. These alterations on the Kyn/Trp ratio may be due to enhanced activity of IDO and/or TDO.…”

Section: Discussionsupporting

confidence: 90%

Low Serum Tryptophan Levels as an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age

Ramos-Chávez

Roldán-Roldán

García-Juárez

et al. 2018

Oxidative Medicine and Cellular Longevity

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Aging is a physiological decline process. The number of older adults is growing around the world; therefore, the incidence of cognitive impairment, dementia, and other diseases related to aging increases. The main cellular factors that converge in the aging process are mitochondrial dysfunction, antioxidant impairment, inflammation, and immune response decline, among others. In this context, these cellular changes have an influence on the kynurenine pathway (KP), the main route of tryptophan (Trp) catabolism. KP metabolites have been involved in the aging process and neurodegenerative diseases. Although there are changes in the metabolite levels with age, at this time, there is no study that has evaluated cognitive decline as a consequence of Trp catabolism fluctuation in aging. The aim of this study was to evaluate the relation between the changes in Trp catabolism and cognitive impairment associated with age through KP metabolites level alterations in women over 50 years of age. Seventy-seven nondemented women over 50 years old were examined with a standardized cognitive screening evaluation in Spanish language (Neuropsi), Beck anxiety inventory (BAI), and the geriatric depression scale (GDS). Also, serum levels of Trp, kynurenine (Kyn), kynurenic acid (KYNA), and 3-hydroykynurenine (3-HK) and the glutathione ratio (GSH/GSSG) were measured. Results showed a negative correlation between age and Trp levels and a positive correlation between age and KYNA/Trp and 3-HK/Trp ratios. The level of cognitive impairment showed a significant positive association with age and with kynurenine pathway activation and a significant negative correlation with Trp levels. The GSH/GSSG ratio correlated positively with Trp levels and negatively with Kyn/Trp and 3-HK/Trp ratios. The depression score correlated negatively with Trp and positively with the 3-HK/Trp ratio. We concluded that KP activation increases with age and it is strongly associated with the level of cognition performance in nondemented women over 50 years of age.

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Section: Discussionsupporting

confidence: 90%

Low Serum Tryptophan Levels as an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age

Ramos-Chávez

Roldán-Roldán

García-Juárez

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…Reduced levels of tryptophan, serotonin, and indolelactic acid suggested that tryptophan degradation was enhanced through the kynurenine pathway in AD. Tryptophan is a precursor of several bioactive compounds including neurotransmitters (e.g., serotonin), and its metabolism plays an important role in regulating neuronal activity and the inflammatory response [ 38 ]. Furthermore, lower plasma tryptophan levels were associated with decreased olfactory function in elderly populations [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Tryptophan is a precursor of several bioactive compounds including neurotransmitters (e.g., serotonin), and its metabolism plays an important role in regulating neuronal activity and the inflammatory response [ 38 ]. Furthermore, lower plasma tryptophan levels were associated with decreased olfactory function in elderly populations [ 38 ]. We observed a continuous decrease in levels of tryptophan and indolelactic acid with the progression of AD.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Metabolic Profile and Potential Biomarkers in the Plasma of Alzheimer’s Disease

Shao¹,

Ouyang²,

Li³

et al. 2020

Aging and disease

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The expending of elderly population worldwide has resulted in a dramatic rise in the incidence of chronic diseases such as Alzheimer's disease (AD). Inadequate understanding of the mechanisms underlying AD has hampered the development of efficient tools for definitive diagnosis and curative interventions. Previous studies have attempted to discover reliable biomarkers of AD, but these biomarkers can only be measured through invasive (neuropathological markers in cerebrospinal fluid) or expensive (positron emission tomography scanning or magnetic resonance imaging) techniques. Metabolomics is a high-throughput technology that can detect and catalog large numbers of small metabolites and may be a useful tool for characterization of AD and identification of biomarkers. In this study, we used ultra-performance liquid chromatography-mass spectrometry based untargeted metabolomics to measure the concentrations of plasma metabolites in a cohort of subjects with AD (n=44) and cognitively normal controls (Ctrl, n=94). The AD group showed marked reductions in levels of polyunsaturated fatty acids, acyl-carnitines, degradation products of tryptophan, and elevated levels of bile acids compared to the Ctrl group. We then validated the results using an independent cohort that included subjects with AD (n=30), mild cognitive impairment (MCI, n=13), healthy controls (n=43), and non-AD neurological disease controls (NDC, n=31). We identified five metabolites comprising cholic acid, chenodeoxycholic acid, allocholic acid, indolelactic acid, and tryptophan that were able to distinguish patients with AD from both Ctrl and NDC with satisfactory sensitivity and specificity. The concentrations of these metabolites were significantly correlated with disease severity. Our results also suggested that altered bile acid profiles in AD and MCI might indicate early risk for the development of AD. These findings may allow for development of new approaches for diagnosis of AD and may provide novel insights into AD pathogenesis.

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“…The plasma samples were deproteinized using acetonitrile at a final concentration of 80.0% before the measurements were performed. The plasma concentrations of 39 human amino acids were measured using high-performance liquid chromatography and electrospray ionization mass spectrometry (HPLC–ESI–MS) (Hitachi High-Technologies, Ibaraki, Japan), followed by pre-column derivatization using previously described analytical methods [26,27,28], and Glu and Gln sample concentrations were used for subsequent analyses.…”

Section: Methodsmentioning

confidence: 99%

Association between Brain and Plasma Glutamine Levels in Healthy Young Subjects Investigated by MRS and LC/MS

et al. 2019

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Both glutamine (Gln) and glutamate (Glu) are known to exist in plasma and brain. However, despite the assumed relationship between brain and plasma, no studies have clarified the association between them. Proton magnetic resonance spectroscopy (MRS) was sequentially performed twice, with a 60-min interval, on 10 males and 10 females using a 3T scanner. Blood samples for liquid chromatography–mass spectrometry (LC/MS) to measure Gln and Glu concentrations in plasma were collected during the time interval between the two MRS sessions. MRS voxels of interest were localized at the posterior cingulate cortex (PCC) and cerebellum (Cbll) and measured by the SPECIAL sequence. Spearman’s correlation coefficient was used to examine the association between brain and plasma metabolites. The Gln concentrations in PCC (mean of two measurements) were positively correlated with Gln concentrations in plasma (p < 0.01, r = 0.72). However, the Glu concentrations in the two regions were not correlated with those in plasma. Consideration of the different dynamics of Gln and Glu between plasma and brain is crucial when addressing the pathomechanism and therapeutic strategies for brain disorders such as Alzheimer’s disease and hepatic encephalopathy.

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Low plasma tryptophan is associated with olfactory function in healthy elderly community dwellers in Japan

Cited by 8 publications

References 30 publications

Low Serum Tryptophan Levels as an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age

Low Serum Tryptophan Levels as an Indicator of Global Cognitive Performance in Nondemented Women over 50 Years of Age

Alteration of Metabolic Profile and Potential Biomarkers in the Plasma of Alzheimer’s Disease

Association between Brain and Plasma Glutamine Levels in Healthy Young Subjects Investigated by MRS and LC/MS

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