Regressive Autism Spectrum Disorder: High Levels of Total Secreted Amyloid Precursor Protein and Secreted Amyloid Precursor Protein-α in Plasma.

Xiaoli Li,Yang Yu,Ying Dai,Bin Peng,Ting Yang,Yupeng Cun,Jie Chen,Xiao Liu,Qian Cheng,Tingyu Li,Ping Zhou,Hua Wei,Qiu Li,Li Chen,Qiongli Fan,Yuping Zhang,Zhiyang Jiang

doi:10.3389/fpsyt.2022.809543

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social communication difficulties, repetitive behaviors, and parochial interests. Individuals with regressive ASD (RA), a unique subtype, have poor outcomes. Moreover, there are currently no validated blood-based biomarkers for ASD, hindering early diagnosis and treatment. This study was the first to examine plasma levels of total secreted amyloid precursor protein (sAPPtotal), secreted amyloid precursor protein-α (sAPPα), and secreted amyloid precursor protein-β (sAPPβ) in children diagnosed with RA (n = 23) and compare them with the levels in age-matched children with non-regressive ASD (NRA) (n = 23) and typically developing (TD) controls (n = 23). We found that sAPPtotal and sAPPα levels were significantly higher in children with RA than in children with NRA or in TD controls. In contrast, no difference was observed in sAPPβ levels. In conclusion, increased plasma levels of sAPPtotal and sAPPα may be valuable biomarkers for the early identification of ASD regression. Prospective studies will be conducted using a larger sample to further investigate these differences.

Highlights

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that emerges in early childhood and is characterized by social communication difficulties, repetitive behaviors, and parochial interests [1]
The sAPPtotal and secreted amyloid precursor protein-α (sAPPα) levels were significantly higher in the regressive ASD (RA) group than in the non-regressive ASD (NRA) and typically developing (TD) groups
The results showed that plasma levels of sAPPtotal and sAPPα were higher in the RA group than in the NRA and TD groups, but there were no significant differences in secreted amyloid precursor protein-β (sAPPβ) levels between any two of the three groups

Summary

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that emerges in early childhood and is characterized by social communication difficulties, repetitive behaviors, and parochial interests [1]. The diagnosis of ASD depends on behavioral descriptions and characteristic observations [6], with the average age at diagnosis being 5 years old [7]. Screening and diagnosis of ASD are very challenging, and the American Academy of Pediatrics recommends that children be screened early and continuously tested before the age of 2 years [9]. Behavioral interventions can improve outcomes, there are no drugs that completely alleviate the symptoms of ASD [10, 11]. Individuals with regressive ASD (RA), a complex subtype of the ASD phenotype, consistently have poor outcomes [12, 13], which may be related to the fact that individuals with RA show poorer language development, more severe autism, and lower intellectual function than those with non-regressive ASD (NRA) [14] as well as to the neurological and pathological bases of regression.

Results

Discussion

Conclusion