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 |
| 卷 | 185 |
| DOIs | |
| 出版狀態 | 已發佈 - 十月 1 2019 |
指紋
ASJC Scopus subject areas
- Biochemistry
- Toxicology
- Pharmacology
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience
引用此文
D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer's disease or mild cognitive impairment. / Lin, Chieh Hsin; Yang, Hui Ting; Lane, Hsien Yuan.
於: Pharmacology Biochemistry and Behavior, 卷 185, 172760, 01.10.2019.研究成果: 雜誌貢獻 › 文章
}
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
UR - http://www.scopus.com/inward/record.url?scp=85070888790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070888790&partnerID=8YFLogxK
U2 - 10.1016/j.pbb.2019.172760
DO - 10.1016/j.pbb.2019.172760
M3 - Article
AN - SCOPUS:85070888790
VL - 185
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
SN - 0091-3057
M1 - 172760
ER -