D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer's disease or mild cognitive impairment.
Pharmacol Biochem Behav
; 185: 172760, 2019 10.
Article
in En
| MEDLINE
| ID: mdl-31422081
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 (râ¯=â¯0.186, pâ¯=â¯0.026) and D-/Total- serine ratio (râ¯=â¯0.191, pâ¯=â¯0.022). ADAS-cog behavior scores were negatively correlated with D-glutamate (râ¯=â¯-0.177, pâ¯=â¯0.034) and L-glutamate (râ¯=â¯-0.250, pâ¯=â¯0.003), but positively correlated with D-alanine (râ¯=â¯0.236, pâ¯=â¯0.005) and D-/Total- alanine ratio (râ¯=â¯0.252, pâ¯=â¯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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Serine
/
Glutamic Acid
/
Alanine
/
Alzheimer Disease
/
Cognitive Dysfunction
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
Pharmacol Biochem Behav
Year:
2019
Document type:
Article
Affiliation country:
Taiwan