Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis

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

The mammals of Angola

Scientific investigations on the mammals of Angola started over 150 years ago, but information remains scarce and scattered, with only one recent published account. Here we provide a synthesis of the mammals of Angola based on a thorough survey of primary and grey literature, as well as recent unpublished records. We present a short history of mammal research, and provide brief information on each species known to occur in the country. Particular attention is given to endemic and near endemic species. We also provide a zoogeographic outline and information on the conservation of Angolan mammals. We found confirmed records for 291 native species, most of which from the orders Rodentia (85), Chiroptera (73), Carnivora (39), and Cetartiodactyla (33). There is a large number of endemic and near endemic species, most of which are rodents or bats. The large diversity of species is favoured by the wide range of habitats with contrasting environmental conditions, while endemism tends to be associated with unique physiographic settings such as the Angolan Escarpment. The mammal fauna of Angola includes 2 Critically Endangered, 2 Endangered, 11 Vulnerable, and 14 Near-Threatened species at the global scale. There are also 12 data deficient species, most of which are endemics or near endemics to the countryinfo:eu-repo/semantics/publishedVersio

Defining novel functions for cerebrospinal fluid in ALS pathophysiology

Despite the considerable progress made towards understanding ALS pathophysiology, several key features of ALS remain unexplained, from its aetiology to its epidemiological aspects. The glymphatic system, which has recently been recognised as a major clearance pathway for the brain, has received considerable attention in several neurological conditions, particularly Alzheimer's disease. Its significance in ALS has, however, been little addressed. This perspective article therefore aims to assess the possibility of CSF contribution in ALS by considering various lines of evidence, including the abnormal composition of ALS-CSF, its toxicity and the evidence for impaired CSF dynamics in ALS patients. We also describe a potential role for CSF circulation in determining disease spread as well as the importance of CSF dynamics in ALS neurotherapeutics. We propose that a CSF model could potentially offer additional avenues to explore currently unexplained features of ALS, ultimately leading to new treatment options for people with ALS.</p