D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer's disease or mild cognitive impairment

Chieh Hsin Lin, Hui Ting Yang, Hsien Yuan Lane

研究成果: 雜誌貢獻文章

摘要

Background: D-amino acids have been recognized as bioactive substances in humans. D-Serine and D-alanine are co-agonists of N-methyl-D-aspartate receptors. Glutamate has been suggested to be involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to explore the roles of amino acids, particularly D-amino acids, in cognitive decline among patients with AD or mild cognitive impairment (MCI). Methods: We enrolled 144 patients: 20 amnestic MCI, 85 mild AD, 25 moderate AD, and 14 severe AD. Serum levels of amino acids were measured by high performance liquid chromatography and confirmed by D-amino acid oxidase assay. The cognitive function was mainly evaluated by Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog). Results: ADAS-cog total scores were positively correlated with D-serine (r = 0.186, p = 0.026) and D-/Total- serine ratio (r = 0.191, p = 0.022). ADAS-cog behavior scores were negatively correlated with D-glutamate (r = −0.177, p = 0.034) and L-glutamate (r = −0.250, p = 0.003), but positively correlated with D-alanine (r = 0.236, p = 0.005) and D-/Total- alanine ratio (r = 0.252, p = 0.002). Among the 11 tasks of ADAS-cog, D-glutamate and D-serine were correlated with different items respectively, noteworthily in the opposite direction. Conclusion: This is the first study suggesting that D-amino acids in blood may be correlated with ADAS-cog in different items and in the opposite direction. Lower D-glutamate and higher D-alanine levels may predict more behavioral symptoms. In summary, D-glutamate, D-serine and D-alanine play different and characteristic roles in AD. Further longitudinal studies are warranted to elucidate the function and interaction of D-amino acids in specific cognitive domains as well as various phases of dementia.

原文英語
文章編號172760
期刊Pharmacology Biochemistry and Behavior
185
DOIs
出版狀態已發佈 - 十月 1 2019

指紋

Alanine
Serine
Glutamic Acid
Alzheimer Disease
Amino Acids
D-Amino-Acid Oxidase
Cognitive Dysfunction
Behavioral Symptoms
N-Methyl-D-Aspartate Receptors
Cognition
High performance liquid chromatography
Longitudinal Studies
Dementia
High Pressure Liquid Chromatography
Assays
Blood
Serum

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

引用此文

@article{454ae7c53acb423b897c196f64e2a899,
title = "D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer's disease or mild cognitive impairment",
abstract = "Background: D-amino acids have been recognized as bioactive substances in humans. D-Serine and D-alanine are co-agonists of N-methyl-D-aspartate receptors. Glutamate has been suggested to be involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to explore the roles of amino acids, particularly D-amino acids, in cognitive decline among patients with AD or mild cognitive impairment (MCI). Methods: We enrolled 144 patients: 20 amnestic MCI, 85 mild AD, 25 moderate AD, and 14 severe AD. Serum levels of amino acids were measured by high performance liquid chromatography and confirmed by D-amino acid oxidase assay. The cognitive function was mainly evaluated by Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog). Results: ADAS-cog total scores were positively correlated with D-serine (r = 0.186, p = 0.026) and D-/Total- serine ratio (r = 0.191, p = 0.022). ADAS-cog behavior scores were negatively correlated with D-glutamate (r = −0.177, p = 0.034) and L-glutamate (r = −0.250, p = 0.003), but positively correlated with D-alanine (r = 0.236, p = 0.005) and D-/Total- alanine ratio (r = 0.252, p = 0.002). Among the 11 tasks of ADAS-cog, D-glutamate and D-serine were correlated with different items respectively, noteworthily in the opposite direction. Conclusion: This is the first study suggesting that D-amino acids in blood may be correlated with ADAS-cog in different items and in the opposite direction. Lower D-glutamate and higher D-alanine levels may predict more behavioral symptoms. In summary, D-glutamate, D-serine and D-alanine play different and characteristic roles in AD. Further longitudinal studies are warranted to elucidate the function and interaction of D-amino acids in specific cognitive domains as well as various phases of dementia.",
keywords = "Alzheimer's disease, D-alanine, D-amino acids, D-glutamate, D-Serine, Mild cognitive impairment, N-methyl-D-aspartate receptor",
author = "Lin, {Chieh Hsin} and Yang, {Hui Ting} and Lane, {Hsien Yuan}",
year = "2019",
month = "10",
day = "1",
doi = "10.1016/j.pbb.2019.172760",
language = "English",
volume = "185",
journal = "Pharmacology, Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer's disease or mild cognitive impairment

AU - Lin, Chieh Hsin

AU - Yang, Hui Ting

AU - Lane, Hsien Yuan

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Background: D-amino acids have been recognized as bioactive substances in humans. D-Serine and D-alanine are co-agonists of N-methyl-D-aspartate receptors. Glutamate has been suggested to be involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to explore the roles of amino acids, particularly D-amino acids, in cognitive decline among patients with AD or mild cognitive impairment (MCI). Methods: We enrolled 144 patients: 20 amnestic MCI, 85 mild AD, 25 moderate AD, and 14 severe AD. Serum levels of amino acids were measured by high performance liquid chromatography and confirmed by D-amino acid oxidase assay. The cognitive function was mainly evaluated by Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog). Results: ADAS-cog total scores were positively correlated with D-serine (r = 0.186, p = 0.026) and D-/Total- serine ratio (r = 0.191, p = 0.022). ADAS-cog behavior scores were negatively correlated with D-glutamate (r = −0.177, p = 0.034) and L-glutamate (r = −0.250, p = 0.003), but positively correlated with D-alanine (r = 0.236, p = 0.005) and D-/Total- alanine ratio (r = 0.252, p = 0.002). Among the 11 tasks of ADAS-cog, D-glutamate and D-serine were correlated with different items respectively, noteworthily in the opposite direction. Conclusion: This is the first study suggesting that D-amino acids in blood may be correlated with ADAS-cog in different items and in the opposite direction. Lower D-glutamate and higher D-alanine levels may predict more behavioral symptoms. In summary, D-glutamate, D-serine and D-alanine play different and characteristic roles in AD. Further longitudinal studies are warranted to elucidate the function and interaction of D-amino acids in specific cognitive domains as well as various phases of dementia.

AB - Background: D-amino acids have been recognized as bioactive substances in humans. D-Serine and D-alanine are co-agonists of N-methyl-D-aspartate receptors. Glutamate has been suggested to be involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to explore the roles of amino acids, particularly D-amino acids, in cognitive decline among patients with AD or mild cognitive impairment (MCI). Methods: We enrolled 144 patients: 20 amnestic MCI, 85 mild AD, 25 moderate AD, and 14 severe AD. Serum levels of amino acids were measured by high performance liquid chromatography and confirmed by D-amino acid oxidase assay. The cognitive function was mainly evaluated by Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog). Results: ADAS-cog total scores were positively correlated with D-serine (r = 0.186, p = 0.026) and D-/Total- serine ratio (r = 0.191, p = 0.022). ADAS-cog behavior scores were negatively correlated with D-glutamate (r = −0.177, p = 0.034) and L-glutamate (r = −0.250, p = 0.003), but positively correlated with D-alanine (r = 0.236, p = 0.005) and D-/Total- alanine ratio (r = 0.252, p = 0.002). Among the 11 tasks of ADAS-cog, D-glutamate and D-serine were correlated with different items respectively, noteworthily in the opposite direction. Conclusion: This is the first study suggesting that D-amino acids in blood may be correlated with ADAS-cog in different items and in the opposite direction. Lower D-glutamate and higher D-alanine levels may predict more behavioral symptoms. In summary, D-glutamate, D-serine and D-alanine play different and characteristic roles in AD. Further longitudinal studies are warranted to elucidate the function and interaction of D-amino acids in specific cognitive domains as well as various phases of dementia.

KW - Alzheimer's disease

KW - D-alanine

KW - D-amino acids

KW - D-glutamate

KW - D-Serine

KW - Mild cognitive impairment

KW - N-methyl-D-aspartate receptor

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