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Depositordc.contributorSpires-Jones, Tara
Funderdc.contributor.otherERC - European Research Councilen_UK
Funderdc.contributor.otherAlzheimer's Research UKen_UK
Funderdc.contributor.otherUniversity of Edinburghen_UK
Funderdc.contributor.otherWellcome Trusten_UK
Funderdc.contributor.otherMND Scotland
Spatial Coveragedc.coverage.spatialUKen
Spatial Coveragedc.coverage.spatialUNITED KINGDOMen
Data Creatordc.creatorHenstridge, Christopher M
Data Creatordc.creatorSpires-Jones, Tara L
Date Accessioneddc.date.accessioned2017-12-13T12:00:05Z
Date Availabledc.date.available2017-12-13T12:00:05Z
Citationdc.identifier.citationHenstridge, Christopher; Spires-Jones, Tara. (2017). Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis - Analysis macros, [software]. University of Edinburgh. https://doi.org/10.7488/ds/2268.en
Persistent Identifierdc.identifier.urihttp://hdl.handle.net/10283/2974
Persistent Identifierdc.identifier.urihttps://doi.org/10.7488/ds/2268
Dataset Description (abstract)dc.description.abstractIn 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. Here we provide the data analysis macros that we generated to analyse the data presented in this paper, along with the manuscript files.en_UK
Languagedc.language.isoengen_UK
Publisherdc.publisherUniversity of Edinburgh. Edinburgh Medical Schoolen_UK
Rightsdc.rightsCreative Commons Attribution 4.0 International Public Licenseen
Subjectdc.subjectALSen_UK
Subjectdc.subjectsynapseen_UK
Subjectdc.subjectarray tomographyen_UK
Subject Classificationdc.subject.classificationNeuroscienceen_UK
Titledc.titleSynapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis - Analysis macrosen_UK
Typedc.typesoftwareen_UK

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