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
N1 - Funding Information:
This work was funded by Ministry of Science and Technology, Taiwan (MOST 105-2314-B-182A-059 -, MOST 107-2628-B-182A-002 -), Kaohsiung Chang Gung Memorial Hospital , Taiwan ( CMRPG8G1391 ), China Medical University Hospital , Taiwan ( DMR-106-099 ) and Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence ( MOHW107-TDU-B-212-123004 ). The aforementioned institutes had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Publisher Copyright:
© 2019 Elsevier Inc.
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 -