ReviewFrontiers in psychiatry2019
Novel Contribution of Secreted Amyloid-β Precursor Protein to White Matter Brain Enlargement in Autism Spectrum Disorder.
Review in Frontiers in psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Prenatal and postnatal effects of gestational immune activation on synaptic and neurodevelopmental pathways via epigenetic mechanisms.Translational psychiatry · 2026Article
- Structural Variant and Repeat Expansion Findings Identified by Optical Genome Mapping in Complex Autism Spectrum Disorder With Concomitant Neurodevelopmental Disorders.Human mutation · 2026Article
- Age-related differences in axon pruning and myelination may alter neural signaling in autism spectrum disorder.Molecular autism · 2025Article
- Age-Dependent Dysregulation of APP in Neuronal and Skin Cells from Fragile X Individuals.Cells · 2023Article
- Extracellular Vesicles in Mental Disorders: A State-of-art Review.International journal of biological sciences · 2023Review
- Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly.Frontiers in molecular neuroscience · 2023Review
- The protective effects of sesamol and/or the probiotic,Frontiers in pharmacology · 2023Article
- Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases.Neural regeneration research · 2022Review
- Frontotemporal neurofibrillary tangles and cerebrovascular lesions are associated with autism spectrum behaviors in late-life dementia.Journal of neurology · 2022Article
- DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders.International journal of molecular sciences · 2022Review
- Comparison of behaviors characteristic of autism spectrum disorder behaviors and behavioral and psychiatric symptoms of dementia.Aging & mental health · 2022Article
- Effects of microRNA-298 on APP and BACE1 translation differ according to cell type and 3'-UTR variation.Scientific reports · 2022Article
- Human microRNA (miR-20b-5p) modulates Alzheimer's disease pathways and neuronal function, and a specific polymorphism close to the MIR20B gene influences Alzheimer's biomarkers.Molecular psychiatry · 2022Article
- Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer's Disease.Biomolecules · 2021Review
- The prevalence and incidence of early-onset dementia among adults with autism spectrum disorder.Autism research : official journal of the International Society for Autism Research · 2021Article
- Proteomics of autism and Alzheimer's mouse models reveal common alterations in mTOR signaling pathway.Translational psychiatry · 2021Article
- Oligodendrocyte lineage cells and depression.Molecular psychiatry · 2021Review
- Identification of Gene Loci That Overlap Between Mental Disorders and Poor Prognosis of Cancers.Frontiers in psychiatry · 2021Article
- The Novel Potential Therapeutic Utility of Montelukast in Alleviating Autistic Behavior Induced by Early Postnatal Administration of Thimerosal in Mice.Cellular and molecular neurobiology · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The most replicated neuroanatomical finding in autism is the tendency toward brain overgrowth, especially in younger children. Research shows that both gray and white matter are enlarged. Proposed mechanisms underlying brain enlargement include abnormal inflammatory and neurotrophic signals that lead to excessive, aberrant dendritic connectivity via disrupted pruning and cell adhesion, and enlargement of white matter due to excessive gliogenesis and increased myelination. Amyloid-β protein precursor (βAPP) and its metabolites, more commonly associated with Alzheimer's disease (AD), are also dysregulated in autism plasma and brain tissue samples. This review highlights findings that demonstrate how one βAPP metabolite, secreted APPα, and the ADAM family α-secretases, may lead to increased brain matter, with emphasis on increased white matter as seen in autism. sAPPα and the ADAM family α-secretases contribute to the anabolic, non-amyloidogenic pathway, which is in contrast to the amyloid (catabolic) pathway known to contribute to Alzheimer disease. The non-amyloidogenic pathway could produce brain enlargement via genetic mechanisms affecting mRNA translation and polygenic factors that converge on molecular pathways (mitogen-activated protein kinase/MAPK and mechanistic target of rapamycin/mTOR), promoting neuroinflammation. A novel mechanism linking the non-amyloidogenic pathway to white matter enlargement is proposed: α-secretase and/or sAPPα, activated by ERK receptor signaling activates P13K/AKt/mTOR and then Rho GTPases favoring myelination via oligodendrocyte progenitor cell (OPC) activation of cofilin. Applying known pathways in AD to autism should allow further understanding and provide options for new drug targets.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.