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Sci Rep. 2016 May 23;6:26052. doi: 10.1038/srep26052.

Finding novel distinctions between the sAPPα-mediated anabolic biochemical pathways in Autism Spectrum Disorder and Fragile X Syndrome plasma and brain tissue.

Author information

1
Indiana University School of Medicine, Departments of Psychiatry, Indianapolis, Indiana-46202, USA.
2
Indiana University School of Medicine, Departments of Neurology, Indianapolis, Indiana-46202, USA.
3
Indiana University School of Medicine, Departments of Medical and Molecular Genetics, Institute of Psychiatric Research, Indianapolis, Indiana-46202, USA.
4
Indiana Alzheimer Disease Center, Indianapolis, Indiana-46202, USA.

Abstract

Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are developmental disorders. No validated blood-based biomarkers exist for either, which impedes bench-to-bedside approaches. Amyloid-β (Aβ) precursor protein (APP) and metabolites are usually associated with Alzheimer's disease (AD). APP cleavage by α-secretase produces potentially neurotrophic secreted APPα (sAPPα) and the P3 peptide fragment. β-site APP cleaving enzyme (BACE1) cleavage produces secreted APPβ (sAPPβ) and intact Aβ. Excess Aβ is potentially neurotoxic and can lead to atrophy of brain regions such as amygdala in AD. By contrast, amygdala is enlarged in ASD but not FXS. We previously reported elevated levels of sAPPα in ASD and FXS vs.

CONTROLS:

We now report elevated plasma Aβ and total APP levels in FXS compared to both ASD and typically developing controls, and elevated levels of sAPPα in ASD and FXS vs.

CONTROLS:

By contrast, plasma and brain sAPPβ and Aβ were lower in ASD vs. controls but elevated in FXS plasma vs.

CONTROLS:

We also detected age-dependent increase in an α-secretase in ASD brains. We report a novel mechanistic difference in APP pathways between ASD (processing) and FXS (expression) leading to distinct APP metabolite profiles in these two disorders. These novel, distinctive biochemical differences between ASD and FXS pave the way for blood-based biomarkers for ASD and FXS.

PMID:
27212113
PMCID:
PMC4876513
DOI:
10.1038/srep26052
[Indexed for MEDLINE]
Free PMC Article

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