Estimation of Alpha-Synuclein Monomer and Oligomer Levels in the Saliva of the Children With Autism Spectrum Disorder: A Possibility for an Early Diagnosis

Abstract

Background In degenerative brain diseases like Parkinson's disease (PD), alpha-synuclein (a-syn) can be in its monomeric (a-syn-mono) or toxic oligomeric (a-syn-oligo) or as a total (a-syn-total) forms in the biological body fluids including saliva. Past research has observed major a-syn plasma variations in children with autism spectrum disorder (ASD) pointing toward brain degenerative components in their pathophysiology. No prior study has shown a-syn levels in ASD patients' saliva. Objective This study estimates the levels of alpha-synuclein monomer (a-syn-mono) and alpha-synuclein oligomer (a-syn-oligo) in the saliva of ASD affected children so that saliva can be a method for detecting disorder. Materials and methods This cross-sectional, multi-center study was conducted in Islamic International Medical College, Autism Resource Centre (ARC), and Step-to-learn Rehabilitation center for the slow learner in Rawalpindi. The research was performed for one year from August 2018 to August 2019. Saliva samples from 80 children (40 ASD affected children, and 40 age- and sex-comparable healthy controls) were collected. Specific anti-alpha-synuclein monomers (anti-a-syn-mono) and anti-alpha-synuclein oligomers (anti-a-syn-oligo) enzyme-linked immunosorbent assay (ELISA) kits analyzed the salivary samples. Mean ± SD were reported for quantitative data. The data between the two groups were compared using an independent t-test. The p-value of ≤ 0.05 was considered statistically significant. Results A total of 80 children were included in the study (n=40 ASD affected, n=40 healthy controls). The age of participating children was between four and eight years. The mean alpha-synuclein monomer level in the saliva of ASD children was 92.03 ± 117.09 pg/ml (p≤0.05), and in healthy subjects was 186.78 ± 239.31 ρg/ml. The levels of alpha-synuclein oligomer in the saliva of patients with ASD children were 0.13 ± 0.05 ng/ml (p<0.001), and in the healthy subjects was 0.33 ± 0.26 ng/ml. Both alpha-synuclein monomer and alpha-synuclein oligomer levels were low in the saliva of ASD children. Conclusion Children with ASD had low levels of alpha-synuclein monomer and oligomer than healthy children which are unique than that of levels found in other degenerative brain diseases.

Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum disorder after consumption of a beta-glucan food supplement in a randomized, parallel-group pilot clinical study

“…The copyright holder for this preprint this version posted June 29, 2021. ; https://doi.org/10.1101/2021.06.28.21259619 doi: medRxiv preprint actually owe their aetiology to alpha-synuclein dysregulation (Kadak et al, 2015;Sriwimol et al, 2018;Obergasteiger et al, 2014). Further, alpha-synuclein has recently been considered one of the important biomarkers for the diagnosis of autism and ASD, wherein the levels are low compared to age-matched controls (Kadak et al, 2015;Sriwimol et al, 2018;Siddique et al 2020). In regard to neurodegenerative diseases such as PD, the reports have been varied, with some reporting lower than normal levels and others higher.…”

Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum disorder after consumption of a beta-glucan food supplement in a randomised, parallel-group pilot clinical study

“…1 2 Alpha-synuclein as a presynaptic neurotransmitter plays a key role in the synaptic functions of neurons by regulating calcium dependent secretion activator 2 (CADPS2) messenger RNA (mRNA) expression. [3][4][5] Alpha-synuclein has already been reported to be associated with several neurodegenerative disorders, collectively called synucleinopathies such as Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. 1 The levels of alpha-synuclein have been variedly reported between ASD and PD wherein in ASD, levels lower than age-matched controls has been reported [3][4][5][6] while in PD, some have reported lower than normal levels and others higher.…”

“…[3][4][5] Alpha-synuclein has already been reported to be associated with several neurodegenerative disorders, collectively called synucleinopathies such as Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. 1 The levels of alpha-synuclein have been variedly reported between ASD and PD wherein in ASD, levels lower than age-matched controls has been reported [3][4][5][6] while in PD, some have reported lower than normal levels and others higher. At present, there is no definitive cure for ASD.…”

“…Synucleins are important in the context of brains and neurons 1 2. Alpha-synuclein as a presynaptic neurotransmitter plays a key role in the synaptic functions of neurons by regulating calcium dependent secretion activator 2 (CADPS2) messenger RNA (mRNA) expression 3–5. Alpha-synuclein has already been reported to be associated with several neurodegenerative disorders, collectively called synucleinopathies such as Alzheimer’s disease (AD), Parkinson’s disease (PD), dementia with Lewy bodies and multiple system atrophy 1.…”

Qualitative Evaluation of α-Synuclein: A Critical Step in Unravelling the Complexities of Autism Spectrum Disorder

“…The role of α-synuclein in neurodevelopmental conditions such as ASD has also been studied [ 1 ]. There are several controversies regarding the evaluation of α-synuclein in ASD based on its source, such as plasma or saliva, although its levels are known to be relevant to disease severity [ 1 , 2 , 3 , 4 ]. Varying levels of α-synuclein in children with ASD compared to normal matched controls have been reported, with some conflictingly reporting increased and decreased plasma levels [ 1 , 2 , 3 ].…”