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.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Henstridge CM,Sideris DI,Carroll E,Rotariu S,Salomonsson S,Tzioras M,McKenzie CA,Smith C,von Arnim CAF,Ludolph AC,Lulé D,Leighton D,Warner J,Cleary E,Newton J,Swingler R,Chandran S,Gillingwater TH,Abrahams S,Spires-doi
10.1007/s00401-017-1797-4subject
Has Abstractpub_date
2018-02-01 00:00:00pages
213-226issue
2eissn
0001-6322issn
1432-0533pii
10.1007/s00401-017-1797-4journal_volume
135pub_type
杂志文章abstract::Adult rabbits were subjected to 4.5 Gy of whole-blody or brain alone gamma-irradiation, and their hippocampus was examined with the light and electron microscope. Pycnotic cells were found at the base of the granular layer of the dentate gyrus in the so-called subgranular zone, as soon as 3 h after irradiation, and we...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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abstract::The recently identified prolactin (PRL)-releasing peptide (PrRP) is the first hypothalamic peptide hormone found to operate as a ligand of an orphan receptor that specifically stimulates PRL production from the pituitary gland. However, its other biological functions remain unknown. Using immunohistochemistry, we exam...
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
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journal_title:Acta neuropathologica
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abstract::Observations have been made on the structure of the paranodal region at nodes of Ranvier in the sural nerve of patients with diabetic sensory polyneuropathy. The structure of the paranodes was examined with particular attention to the definition and assessment of axoglial dysjunction, which has been claimed to be a ch...
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