Effect of ALDH2 on Sleep Disturbances in Patients with Parkinson\u2019s Disease

Chia-Yen Lin,Rwei-Ling Yu,Ruey-Meei Wu,Chun-Hsiang Tan

doi:10.1038/s41598-019-55427-w

Abstract

Monoamine neurotransmitters play essential roles in the regulation of arousal and sleep. Impaired metabolism of monoamine neurotransmitters could result in the accumulation of neurotoxic aldehyde metabolites and, hence, neuronal degeneration. Aldehyde dehydrogenases play an important role in the metabolism of the neurotoxic aldehyde metabolites, including the aldehyde metabolites of dopamine, serotonin, and noradrenaline. Deficient aldehyde dehydrogenase 2 (ALDH2) has been suggested to result in the accumulation of these biogenic aldehydes. An ALDH2 single nucleotide polymorphism (SNP), rs671 (A), results in significantly reduced ALDH2 enzyme activity. A total of 83 Parkinson’s disease (PD) patients were recruited in this study. In addition to the genotypes of rs671, the patients were assessed with the PD sleep scale-2nd version (PDSS-2) and the Epworth sleepiness scale (ESS) for symptoms of daytime and nocturnal sleep disturbances. The patients carrying rs671 (A) had more frequent dozing while lying down to rest in the afternoon (ESS item5) (F = 7.308, p = 0.008) than the rs671 (GG) patients. The patients with rs671 (A) reported a trend toward more frequent difficulty staying asleep than the patients with rs671 (GG). (F = 3.278, p = 0.074). The results indicate that patients carrying allele rs671 (A) are more likely to experience impairment in the regulation of arousal and sleep. The results also support the hypothesis that the accumulation of neurotoxic monoamine neurotransmitter aldehyde metabolites secondary to reduced ALDH2 enzyme activity may cause more severe monoaminergic neuronal loss and, hence, more severe symptoms in the regulation of wakefulness and sleep.

Highlights

Parkinson’s disease (PD) is a common neurodegenerative disorder
There were no significant differences in age, gender, education years, age at onset[19,20], disease duration, levodopa equivalent daily dose (LED), levodopa equivalent dose attributable to dopamine agonist, disease severity (Hoehn and Yahr stage, H&Y stage) and severity of motor symptoms between the two groups (Table 1)
In terms of daytime sleepiness, which was evaluated with Epworth sleepiness scale (ESS) scale, there was a significant difference in the ESS item 5 (Table 2)

Summary

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disorder. A meta-analysis of the worldwide data showed increasing prevalence with age, and the prevalence was suggested to be 1,087 and 1,903 per 100,000 persons among those between 70 to years of age and those above years of age, respectively[1]. The biogenic aldehyde products of dopamine, noradrenaline, and serotonin through the metabolism of monoamine oxidase (MAO) are 3,4-dihydroxyphenylacetaldehyde (DOPAL), 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) and 5-hydroxyindole-3-acetaldehyde (5-HIAL), respectively. These monoaminergic aldehydes may accumulate under the circumstances of ALDH2 deficiency[11,12]. Almost half of the population in south Han Chinese and Japanese carries the impaired enzyme phenotype[14] Results obtained from both in vitro and in vivo experiments suggest that the accumulation of these monoamine-degraded aldehydes can lead to neurotoxicity[12,15,16,17]. We investigated whether ALDH2 deficiency secondary to rs[671] (A) can cause sleep disturbances in patients with PD to gain a deeper understanding of the impact of monoamine neurotransmitters in the sleep-awake system regulation and the effect of rs[671] (A) on the non-motor symptoms of PD patients

Methods

Results

Conclusion