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Neuropediatrics 2015; 46(06): 410-415
DOI: 10.1055/s-0035-1565273
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Low Serum Level α-Synuclein and Tau Protein in Autism Spectrum Disorder Compared to Controls

Muhammed Tayyib Kadak
1   Department of Child and Adolescent Psychiatry, Cerrahpaşa School of Medicine, Istanbul University, Istanbul, Turkey
,
Ihsan Cetin
2   Department of Nutrition and Dietetics, School of Health, Batman University, Batman, Turkey
,
Mahmut Cem Tarakçıoğlu
3   Clinics of Child and Adolescent Psychiatry, Bakırköy Dr Sadi Konuk Training and Education Hospital, Istanbul, Turkey
,
Ömer Faruk Özer
4   Department of Biochemistry, Bezmi Alem Vakıf University, Istanbul, Turkey
,
Selma Kaçar
5   Department of Psychiatry, Cerrahpaşa School of Medicine, Istanbul University, Istanbul, Turkey
,
Behzat Çimen
6   Department of Biochemistry, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey
› Author Affiliations
Further Information

Publication History

27 May 2015

23 August 2015

Publication Date:
19 October 2015 (online)

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Abstract

α-Synuclein (α-syn) and tau proteins are thought to be related with the synaptic loss and cell death underlying several important neurodegenerative diseases. The aim of our study was to investigate serum α-syn and tau levels in autism. Serum levels of α-syn and tau were measured, and autism spectrum disorder (ASD) severity was assessed at admission using the Childhood Autism Rating Scale (CARS) total score. The mean CARS score of the autism group on admission was 47.91 points (SD: 5.97). The results indicated that the mean serum α-syn and serum tau levels were significantly (p < 0.001) lower in children with ASD as compared with normal cases (33.01 ± 20.78 and 55.19 ± 15.34 ng/mL and 241.23 ± 290.5 and 509.78 ± 269.25 ng/mL, respectively). There was a significant positive correlation between serum α-syn levels and serum levels of tau identified by Pearson correlation analysis (r = 0.922, n = 28, p < 0.001). Synaptic abnormality in autism may result from microglial activity. Furthermore, α-syn and tau aggregation may lead to synaptic dysfunction, and this may contribute to either neuronal or synaptic dysfunction or neurodegeneration. Our preliminary study suggests that low levels of serum α-syn and tau may be implicated in the relationship between synaptic activity and autism.

Keywords

α-synuclein - tau - autism - synucleinopathy
 

  • References

  • 1 Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-Döring F, Trenkwalder C, Schlossmacher MG. α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 2011; 10 (3) 230-240
    CrossrefPubMedGoogle Scholar
  • 2 Sengupta U, Guerrero-Muñoz MJ, Castillo-Carranza DL , et al. Pathological interface between oligomeric alpha-synuclein and tau in synucleinopathies. Biol Psychiatry 2015; ;pii:S0006–3223(15)00003–00007. doi:10.1016/j.biopsych.2014.12.019
    PubMedGoogle Scholar
  • 3 Sui YT, Bullock KM, Erickson MA, Zhang J, Banks WA. Alpha synuclein is transported into and out of the brain by the blood-brain barrier. Peptides 2014; 62: 197-202
    CrossrefPubMedGoogle Scholar
  • 4 Cheng F, Vivacqua G, Yu S. The role of α-synuclein in neurotransmission and synaptic plasticity. J Chem Neuroanat 2011; 42 (4) 242-248
    CrossrefPubMedGoogle Scholar
  • 5 El-Agnaf OMA, Irvine GB. Review: formation and properties of amyloid-like fibrils derived from alpha-synuclein and related proteins. J Struct Biol 2000; 130 (2–3) 300-309
    CrossrefPubMedGoogle Scholar
  • 6 Lee PH, Lee G, Park HJ, Bang OY, Joo IS, Huh K. The plasma alpha-synuclein levels in patients with Parkinson's disease and multiple system atrophy. J Neural Transm 2006; 113 (10) 1435-1439
    CrossrefPubMedGoogle Scholar
  • 7 Duran R, Barrero FJ, Morales B, Luna JD, Ramirez M, Vives F. Plasma alpha-synuclein in patients with Parkinson's disease with and without treatment. Mov Disord 2010; 25 (4) 489-493
    CrossrefPubMedGoogle Scholar
  • 8 Li QX, Mok SS, Laughton KM , et al. Plasma alpha-synuclein is decreased in subjects with Parkinson's disease. Exp Neurol 2007; 204 (2) 583-588
    CrossrefPubMedGoogle Scholar
  • 9 Hong Z, Shi M, Chung KA , et al. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain 2010; 133 (Pt 3): 713-726
    CrossrefPubMedGoogle Scholar
  • 10 Miller DW, Hague SM, Clarimon J , et al. Alpha-synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication. Neurology 2004; 62 (10) 1835-1838
    CrossrefPubMedGoogle Scholar
  • 11 Desplats P, Lee HJ, Bae EJ , et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci U S A 2009; 106 (31) 13010-13015
    CrossrefPubMedGoogle Scholar
  • 12 Roy B, Jackson GR. Interactions between tau and α-synuclein augment neurotoxicity in a drosophila model of Parkinson's disease. Hum Mol Genet 2014; 23 (11) 3008-3023
    CrossrefPubMedGoogle Scholar
  • 13 Parellada M, Penzol MJ, Pina L , et al. The neurobiology of autism spectrum disorders. Eur Psychiatry 2014; 29 (1) 11-19
    CrossrefPubMedGoogle Scholar
  • 14 Schulz-Schaeffer WJ. The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia. Acta Neuropathol 2010; 120 (2) 131-143
    CrossrefPubMedGoogle Scholar
  • 15 Kramer ML, Schulz-Schaeffer WJ. Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci 2007; 27 (6) 1405-1410
    CrossrefPubMedGoogle Scholar
  • 16 Nikolaus S, Antke C, Müller HW. In vivo imaging of synaptic function in the central nervous system: I. Movement disorders and dementia. Behav Brain Res 2009; 204 (1) 1-31
    CrossrefPubMedGoogle Scholar
  • 17 Shipton OA, Leitz JR, Dworzak J , et al. Tau protein is required for amyloid beta-induced impairment of hippocampal long-term potentiation. J Neurosci 2011; 31 (5) 1688-1692
    CrossrefPubMedGoogle Scholar
  • 18 Pozueta J, Lefort R, Shelanski ML. Synaptic changes in Alzheimer's disease and its models. Neuroscience 2013; 251: 51-65
    CrossrefPubMedGoogle Scholar
  • 19 Baykara B, Gencer Ö, İlkin Z, Miral S. Neurocognitive features of the frontal lobe in parents of autistic children [in Turkish]. Turk Psikiyatri Derg 2008; 19 (3) 225-234
    PubMedGoogle Scholar
  • 20 Borghi R, Marchese R, Negro A , et al. Full length alpha-synuclein is present in cerebrospinal fluid from Parkinson's disease and normal subjects. Neurosci Lett 2000; 287 (1) 65-67
    CrossrefPubMedGoogle Scholar
  • 21 El-Agnaf OM, Salem SA, Paleologou KE , et al. Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma. FASEB J 2003; 17 (13) 1945-1947
    PubMedGoogle Scholar
  • 22 Totterdell S, Meredith GE. Localization of alpha-synuclein to identified fibers and synapses in the normal mouse brain. Neuroscience 2005; 135 (3) 907-913
    CrossrefPubMedGoogle Scholar
  • 23 Chandra S, Gallardo G, Fernández-Chacón R, Schlüter OM, Südhof TC. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 2005; 123 (3) 383-396
    CrossrefPubMedGoogle Scholar
  • 24 Fortin DL, Troyer MD, Nakamura K, Kubo S, Anthony MD, Edwards RH. Lipid rafts mediate the synaptic localization of alpha-synuclein. J Neurosci 2004; 24 (30) 6715-6723
    CrossrefPubMedGoogle Scholar
  • 25 Jo E, Darabie AA, Han K, Tandon A, Fraser PE, McLaurin J. alpha-Synuclein-synaptosomal membrane interactions: implications for fibrillogenesis. Eur J Biochem 2004; 271 (15) 3180-3189
    CrossrefPubMedGoogle Scholar
  • 26 Di Rosa G, Puzzo D, Sant'Angelo A, Trinchese F, Arancio O. Alpha-synuclein: between synaptic function and dysfunction. Histol Histopathol 2003; 18 (4) 1257-1266
    PubMedGoogle Scholar
  • 27 Liu S, Ninan I, Antonova I , et al. alpha-Synuclein produces a long-lasting increase in neurotransmitter release. EMBO J 2004; 23 (22) 4506-4516
    CrossrefPubMedGoogle Scholar
  • 28 Al-Wandi A, Ninkina N, Millership S, Williamson SJ, Jones PA, Buchman VL. Absence of alpha-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice. Neurobiol Aging 2010; 31 (5) 796-804
    CrossrefPubMedGoogle Scholar
  • 29 Lotharius J, Brundin P. Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Hum Mol Genet 2002; 11 (20) 2395-2407
    CrossrefPubMedGoogle Scholar
  • 30 Sidhu A, Wersinger C, Vernier P. Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse?. FASEB J 2004; 18 (6) 637-647
    CrossrefPubMedGoogle Scholar
  • 31 Yavich L, Tanila H, Vepsäläinen S, Jäkälä P. Role of alpha-synuclein in presynaptic dopamine recruitment. J Neurosci 2004; 24 (49) 11165-11170
    CrossrefPubMedGoogle Scholar
  • 32 Hutsler JJ, Zhang H. Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. Brain Res 2010; 1309: 83-94
    CrossrefPubMedGoogle Scholar
  • 33 Nguyen M, Roth A, Kyzar EJ , et al. Decoding the contribution of dopaminergic genes and pathways to autism spectrum disorder (ASD). Neurochem Int 2014; 66: 15-26
    CrossrefPubMedGoogle Scholar
  • 34 Garber K. Neuroscience. Autism's cause may reside in abnormalities at the synapse. Science 2007; 317 (5835) 190-191
    CrossrefPubMedGoogle Scholar
  • 35 Zoghbi HY. Postnatal neurodevelopmental disorders: meeting at the synapse?. Science 2003; 302 (5646) 826-830
    CrossrefPubMedGoogle Scholar
  • 36 Morgan JT, Chana G, Pardo CA , et al. Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry 2010; 68 (4) 368-376
    CrossrefPubMedGoogle Scholar
  • 37 Scarr E, Dean B. Altered neuronal markers following treatment with mood stabilizer and antipsychotic drugs indicate an increased likelihood of neurotransmitter release. Clin Psychopharmacol Neurosci 2012; 10 (1) 25-33
    CrossrefPubMedGoogle Scholar
  • 38 Chadchankar H, Yavich L. Sub-regional differences and mechanisms of the short-term plasticity of dopamine overflow in striatum in mice lacking alpha-synuclein. Brain Res 2011; 1423: 67-76
    CrossrefPubMedGoogle Scholar