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pLG72 levels increase in early phase of Alzheimer's disease but decrease in late phase
Chieh-Hsin Lin1,2,3, Chih-Chiang Chiu4,5, Chiung-Hsien Huang6
1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Abstract:
pLG72, named as D-amino acid oxidase activator (although it is not an activator of D-amino acid oxidase demonstrated by later studies), in mitochondria has been regarded as an important modulator of D-amino acid oxidase that can regulate the N-methyl-D-aspartate receptor (NMDAR). Both oxidative stress in mitochondria and NMDAR neurotransmission play essential roles in the process of neurodegenerative dementia. The aim of the study was to investigate whether pLG72 levels changed with the severity of neurodegenerative dementia. We enrolled 376 individuals as the overall cohort, consisting of five groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild Alzheimer's disease [AD], moderate AD, and severe AD. pLG72 levels in plasma were measured using Western blotting. The severity of cognitive deficit was principally evaluated by Clinical Dementia Rating Scale. A gender- and age- matched cohort was selected to elucidate the effects of gender and age. pLG72 levels increased in the MCI and mild AD groups when compared to the healthy group. However, pLG72 levels in the moderate and severe AD groups were lower than those in the mild AD group. D-serine level and D- to total serine ratio were significantly different among the five groups. L-serine levels were correlated with the pLG72 levels. The results in the gender- and age- matched cohort were similar to those of the overall cohort. The finding supports the hypothesis of NMDAR hypofunction in early-phase dementia and NMDAR hyperfunction in late-phase dementia. Further studies are warranted to test whether pLG72 could reflect the function of NMDAR.
Insights
Plasma pLG72 levels initially rise in mild cognitive impairment and early Alzheimer's disease, then decrease in later stages, suggesting a role in neurodegenerative dementia progression and N-methyl-D-aspartate receptor (NMDAR) function.
Area of Science:
- Neuroscience
- Biochemistry
- Gerontology
Background:
- Mitochondrial pLG72 is implicated in regulating N-methyl-D-aspartate receptors (NMDARs).
- Oxidative stress and NMDAR dysfunction are key factors in neurodegenerative dementia.
Purpose of the Study:
- To investigate the relationship between pLG72 levels and the severity of neurodegenerative dementia.
- To explore potential links between pLG72, D-serine, and NMDAR function in dementia.
Main Methods:
- Western blotting was used to measure plasma pLG72 levels in 376 participants across five groups: healthy elderly, mild cognitive impairment (MCI), mild, moderate, and severe Alzheimer's disease (AD).
- Clinical Dementia Rating Scale assessed cognitive deficit severity.
- A gender- and age-matched cohort was analyzed to control for these variables.
Main Results:
- pLG72 levels were elevated in MCI and mild AD groups compared to healthy controls.
- pLG72 levels decreased in moderate and severe AD groups.
- Significant differences in D-serine levels and D- to total serine ratio were observed across groups; L-serine levels correlated with pLG72.
Conclusions:
- pLG72 levels vary with dementia severity, supporting a biphasic role in NMDAR function (hypofunction in early stages, hyperfunction in late stages).
- Further research is needed to confirm pLG72 as a biomarker for NMDAR function in dementia.