Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 185, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2019.172760
Keywords
D-amino acids; D-glutamate; D-Serine; D-alanine; N-methyl-D-aspartate receptor; Alzheimer's disease; Mild cognitive impairment
Funding
- 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]
- Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence [MOHW107-TDU-B-212-123004]
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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.
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