Faculty Opinions recommendation of Benzoate, a D-amino acid oxidase inhibitor, for the treatment of early-phase Alzheimer disease: a randomized, double-blind, placebo-controlled trial.

Objective: Sodium benzoate, a D-amino acid oxidase (DAAO) inhibitor, improved cognitive function of early-phase Alzheimer’s disease (AD) after 24-week treatment. This study examined benzoate treatment for behavioral and psychological symptoms of dementia (BPSD). Methods: In a double-blind, 6-week trial, 97 patients with BPSD were randomized to receive placebo or benzoate (mean dose: 622.0 mg/day). The primary outcomes were ADAS-cog and BEHAVE-AD. Results: Two treatments showed similar safety and primary and secondary outcomes. Conclusions: Compared to antecedent 24-week, higher-dose treatment for early-phase AD, benzoate appeared ineffective in this 6-week trial. Longer-duration, higher-dose trials are warranted to clarify its efficacy for BPSD.

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pLG72 levels increase in early phase of Alzheimer’s disease but decrease in late phase

Scientific Reports ◽

10.1038/s41598-019-49522-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Chieh-Hsin Lin ◽

Chih-Chiang Chiu ◽

Chiung-Hsien Huang ◽

Hui-Ting Yang ◽

Hsien-Yuan Lane

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amino Acid ◽

Early Phase ◽

Late Phase ◽

Acid Oxidase ◽

Matched Cohort ◽

Amino Acid Oxidase ◽

Gender And Age ◽

Neurodegenerative Dementia

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.

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