ArticleActa neuropathologica2018
Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis.
Article in Acta neuropathologica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- The effect of repetitive transcranial magnetic stimulation on immediate and long-term cognitive functions in Alzheimer's dementia and mild cognitive impairment: a meta-analysis.Journal of neuroengineering and rehabilitation · 2025Pooled it
- Human brain pathology in myotonic dystrophy type 1: A systematic review.Neuropathology : official journal of the Japanese Society of Neuropathology · 2021Pooled it
- Distinct cellular phenotypes of language and executive decline in amyotrophic lateral sclerosis.Cell · 2026Article
- King's stages of amyotrophic lateral sclerosis: an 18F-FDG-PET study of brain connectivity.Brain : a journal of neurology · 2026Article
- Associations of cognitive and behavioural impairment in ALS with brain pathology: pTDP-43 versus microglial activation.Journal of neurology · 2026Article
- Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Aberrant CDK4/6-driven cell-cycle reentry drives neuronal loss and defines a therapeutic target in C9orf72 ALS/FTD.iScience · 2026Article
- Pathological TDP-43 filaments accumulate at synapses and cause synaptic dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Amygdala TDP-43 pathology is associated with behavioural dysfunction and ferritin accumulation in amyotrophic lateral sclerosis.Brain communications · 2026Article
- Review
- Bioinformatics Analysis of Persistent Dysregulated Expression of Genes Involved in HCV-Induced Neurological Disorders and Liver Injuries After DAA Treatment Through Weighted Gene Co-Expression Network Analysis.Health science reports · 2025Article
- Synaptopathy in the TDP-43ΔNLS Mouse Model of Sporadic Amyotrophic Lateral Sclerosis.The European journal of neuroscience · 2025Article
- Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress.Cells · 2025Review
- Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.Nature reviews. Neurology · 2025Review
- The spectrum of behavioral disorders in amyotrophic lateral sclerosis: current view.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- The Basis of Cognitive and Behavioral Dysfunction in Amyotrophic Lateral Sclerosis.Brain and behavior · 2024Review
- Distinct Longitudinal Changes in EEG Measures Reflecting Functional Network Disruption in ALS Cognitive Phenotypes.Brain topography · 2024Article
- Effects of different modalities of transcranial magnetic stimulation on post-stroke cognitive impairment: a network meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- RNA editing regulates glutamatergic synapses in the frontal cortex of a molecular subtype of Amyotrophic Lateral Sclerosis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
In addition to motor neurone degeneration, up to 50% of amyotrophic lateral sclerosis (ALS) patients present with cognitive decline. Understanding the neurobiological changes underlying these cognitive deficits is critical, as cognitively impaired patients exhibit a shorter survival time from symptom onset. Given the pathogenic role of synapse loss in other neurodegenerative diseases in which cognitive decline is apparent, such as Alzheimer's disease, we aimed to assess synaptic integrity in the ALS brain. Here, we have applied a unique combination of high-resolution imaging of post-mortem tissue with neuropathology, genetic screening and cognitive profiling of ALS cases. Analyses of more than 1 million synapses using two complimentary high-resolution techniques (electron microscopy and array tomography) revealed a loss of synapses from the prefrontal cortex of ALS patients. Importantly, synapse loss was significantly greater in cognitively impaired cases and was not due to cortical atrophy, nor associated with dementia-associated neuropathology. Interestingly, we found a trend between pTDP-43 pathology and synapse loss in the frontal cortex and discovered pTDP-43 puncta at a subset of synapses in the ALS brains. From these data, we postulate that synapse loss in the prefrontal cortex represents an underlying neurobiological substrate of cognitive decline in ALS.
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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.