RESUMEN
In the last decades, prevalence of autism spectrum disorder (ASD) has been on the rise. However, clear aetiology is still elusive and improvements in early diagnosis are needed. To uncover possible biomarkers present in ASD, we used two-dimensional polyacrylamide gel electrophoresis and nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS), to compare salivary proteome profiling of children with ASD and controls. A total of 889 spots were compared and only those spots with a fold change ≥1.7 and a P-value <0.05 or a fold change of ≥3.0 between ASD cases and controls were analysed by nanoLC-MS/MS. Alpha-amylase, CREB-binding protein, p532, Transferrin, Zn alpha2 glycoprotein, Zymogen granule protein 16, cystatin D and plasminogen were down-regulated in ASD. Increased expression of proto-oncogene Frequently rearranged in advanced T-cell lymphomas 1 (FRAT1), Kinesin family member 14, Integrin alpha6 subunit, growth hormone regulated TBC protein 1, parotid secretory protein, Prolactin-inducible protein precursor, Mucin-16, Ca binding protein migration inhibitory factor-related protein 14 (MRP14) was observed in individuals with ASD. Many of the identified proteins have previously been linked to ASD or were proposed as risk factors of ASD at the genetic level. Some others are involved in pathological pathways implicated in ASD causality such as oxidative stress, lipid and cholesterol metabolism, immune system disturbances and inflammation. These data could contribute to protein signatures for ASD presence, risk and subtypes, and advance understanding of ASD cause as well as provide novel treatment targets for ASD.
Asunto(s)
Trastorno del Espectro Autista , Electroforesis en Gel Bidimensional , Proteínas y Péptidos Salivales/análisis , Espectrometría de Masas en Tándem , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/metabolismo , Niño , Humanos , Proteoma , Proto-Oncogenes Mas , Sensibilidad y EspecificidadRESUMEN
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects approximately 1/68 children, with a more recent study suggesting numbers as high as 1/36. According to Diagnostic and Statistical Manual of Mental Disorders, the etiology of ASD is unknown and diagnosis of this disorder is behavioral. There is currently no biomarker signature for ASD, however, identifying a biomarker signature is crucial as it would aid in diagnosis, identifying treatment targets, monitoring treatments, and identifying the etiology of the disorder. Here we used nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to investigate the saliva from individuals with ASD and matched controls in a 14 vs 14 study. We found numerous proteins to have statistically significant dysregulations, including lactotransferrin, transferrin, polymeric immunoglobulin receptor, Ig A L, Ig J chain, mucin 5 AC, and lipocalin 1 isoform X1. These findings are consistent with previous studies by our lab, and others, and point to dysregulations in the immune system, lipid metabolism and/or transport, and gastrointestinal disturbances, which are common and reoccurring topics in ASD research.
Asunto(s)
Trastorno del Espectro Autista , Niño , Humanos , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/metabolismo , Espectrometría de Masas en Tándem , Proteómica , Biomarcadores , SalivaRESUMEN
Alternate forms of neuropsychological instruments are often made parallel by developing tests with similar numbers of items, formats, and psychometric properties. The present study offers an alternative approach by examining three different trail-making tests that could potentially be used as alternate forms. Over a 3-week period, the Trail Making Test of the Delis-Kaplan Executive Functioning System (DK-TMT), Comprehensive Trail Making Test (CTMT), and Connections Task (CT) were individually administered to 154 undergraduate psychology students in each of six possible orders. Consistent with hypotheses, the three tests share the same underlying factors of sequencing and shifting as alternatives to one- and three-factor models; statistical evidence is provided to support that the two-factor solution is invariant regardless of test order. These findings support the notion that three different trail-making tests can be administered without discernable practice effects, increasing the flexibility of a serial neuropsychological assessment battery.