Significant Changes in Plasma Alpha-Synuclein and Beta-Synuclein Levels in Male Children with Autism Spectrum Disorder

Abstract

Alpha-synuclein (α-synuclein) and beta-synuclein (β-synuclein) are presynaptic proteins playing important roles in neuronal plasticity and synaptic vesicle regulation. To evaluate the association of these two proteins and autism spectrum disorder (ASD), we investigated the plasma α-synuclein and β-synuclein levels in 39 male children with ASD (2 subgroups: 25 autism and 14 pervasive developmental disorder-not otherwise specified (PDD-NOS)) comparing with 29 sex- and age-matched controls by using enzyme-linked immunosorbent assay (ELISA). We first determined the levels of these two proteins in the ASD subgroups and found that there were no significant differences in both plasma α-synuclein and β-synuclein levels in the autism and PDD-NOS groups. Thus, we could combine the 2 subgroups into one ASD group. Interestingly, the mean plasma α-synuclein level was significantly lower (P < 0.001) in the ASD children (10.82 ± 6.46 ng/mL) than in the controls (29.47 ± 18.62 ng/mL), while the mean plasma β-synuclein level in the ASD children (1344.19 ± 160.26 ng/mL) was significantly higher (P < 0.05) than in the controls (1219.16 ± 177.10 ng/mL). This is the first study examining the associations between α-synuclein and β-synuclein and male ASD patients. We found that alterations in the plasma α-synuclein and β-synuclein levels might be implicated in the association between synaptic abnormalities and ASD pathogenesis.

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

“…A study by Kadak et al [ 23 ] found a low serum level of a-syn in ASD children (mean values 33.01 ± 20.78 ng/ml) compared to controls (mean values 241.23 ± 290.5 ng/ml). Sriwimol and Limprasert [ 13 ] in another study done on 39 ASD male children, confirms the observation of significantly lower plasma a-syn-mono levels (mean values 10.82 ± 6.46 ng/ml) in the plasma of ASD children compared to healthy controls (mean values 29.47 ± 18.82 ng/ml). The present study on the saliva of 40 ASD children comprising both male and female subjects not only supports the results mentioned above but also establishes the importance and usability of “saliva” as an essential body secretion.…”

“…In degenerative diseases like PD a-syn-mono becomes abnormally aggregated into a-synuclein oligomers (a-syn-oligo), which is then converted into amyloid fibrils an ultimate precursor of Lewy bodies [ 15 ]. This fact establishes that a-syn-oligo is the main neurotoxic form of a-syn [ 13 ]. A-syn-oligo is present in CSF, plasma, peripheral nerve fibers, gut, skin, and salivary glands and saliva of PD patients [ 16 ].…”

“…In PD, a-synuclein (a-syn) is detectable in the cerebrospinal fluid (CSF), blood, and saliva [ 12 ]. Changes in plasma a-syn levels are also observed in children with ASD, which indicate synaptic dysfunctions in these cases [ 13 ]. In physiological conditions, a-syn is present in the cells as a monomeric form (a-syn-mono) [ 14 ].…”

Serum α-synuclein and IL-1β are increased and correlated with measures of disease severity in children with epilepsy: potential prognostic biomarkers?

“…In recent studies of children with autism spectrum disorder [39] and with attention-deficit/hyperactivity disorder, serum α-synuclein levels are reported to be low or no changes compared to controls [40]. Therefore serum α-synuclein levels may suggest neurodegenerative process related with neuroinflammation in children.…”

The Role of Alpha-Synuclein And Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders

“…A study in 39 children with ASD (age 2-8 years) without known karyotypic abnormalities showed a significant 3-fold decrease in α-syn plasma levels versus controls, which links one of the key proteins in PD pathogenesis to ASD. In this study, beta-synuclein (β-syn) levels were also found to be significantly higher in ASD children compared control group, postulating a compensatory effect of β-syn [68]. This overlapping clinical phenomenology of motor and non-motor symptoms and molecular link between ASD and PD point towards potentially converging disease mechanisms and imbalances of dopamine signaling in the basal ganglia.…”