ReviewNeurology2011
Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links.
Review in Neurology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.
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
86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 143 citations in OpenAlex.
- Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review.Neurology · 2024Pooled it
- Neurodevelopmental Clues to Neurodegeneration.Pediatric neurology · 2021Pooled it
- FMRP Regulates NrCAM Expression via β-catenin and Modulates PSD95, Dendritic Spines and Autism-like Behaviors.Neuroscience bulletin · 2026Article
- Autism and Neurodegeneration: Distinct Disorders or a Shared Biological Continuum?Brain sciences · 2026Review
- Structure-Guided Discovery of Benzoic-Acid-Based TRPC6 Ligands: An Integrated Docking, MD, and MM-GBSA SAR Study: Potential Therapeutic Molecules for Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Spontaneous glutamate release activates mGluR signaling to drive rapid antidepressant responses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular switch of the dendrite-to-spine transport of TDP-43/FMRP-bound neuronal mRNAs and its impairment in ASD.Cellular & molecular biology letters · 2025Article
- Does Bisphenol A (BPA) Exposure Cause Human Diseases?Biomedicines · 2024Review
- C G composition in transposon-derived genes is increased in FXD with perturbed immune system.NAR molecular medicine · 2024Article
- Social Communication Delay in an Unbiased Sample of Preschoolers With theJournal of speech, language, and hearing research : JSLHR · 2024Article
- Genome-wide epistasis analysis reveals gene-gene interaction network on an intermediate endophenotype P-tau/AβScientific reports · 2024Article
- The novel peptide LCGM-10 attenuates metabotropic glutamate receptor 5 activity and demonstrates behavioral effects in animal models.Frontiers in behavioral neuroscience · 2024Article
- Review
- Axonal and presynaptic FMRP: Localization, signal, and functional implications.Hearing research · 2023Review
- Blockade of Type 2A Protein Phosphatase Signaling Attenuates Complement C1q-Mediated Microglial Phagocytosis of Glutamatergic Synapses Induced by Amyloid Fibrils.Molecular neurobiology · 2023Article
- Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly.Frontiers in molecular neuroscience · 2023Review
- APPlications of amyloid-β precursor protein metabolites in macrocephaly and autism spectrum disorder.Frontiers in molecular neuroscience · 2023Review
- Review
- Leveraging gene co-regulation to identify gene sets enriched for disease heritability.American journal of human genetics · 2022Article
- Identification of hub genes and molecular pathways in human T-lymphotropic virus type 1 associated diseases using protein-protein interactions networks.Iranian journal of microbiology · 2022Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The present review highlights an association between autism, Alzheimer disease (AD), and fragile X syndrome (FXS). We propose a conceptual framework involving the amyloid-β peptide (Aβ), Aβ precursor protein (APP), and fragile X mental retardation protein (FMRP) based on experimental evidence. The anabolic (growth-promoting) effect of the secreted α form of the amyloid-β precursor protein (sAPPα) may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPα levels associate with more severe symptoms of autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 (mGluR5). Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPα level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPα and production of insoluble Aβ would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism.
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.