Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS

Show simple item record Waters Sarah en Dieriks Birger en Swanson Molly en Zhang Yibin en Grimsey Natasha en Murray Helen en Turner Clinton en Waldvogel Henry en Faull Richard LM en An Jiyan en Bowser Robert en Curtis Maurice en Dragunow Mike en Scotter Emma en 2020-10-12T01:05:24Z 2020-10-12T01:05:24Z 2019-7-26 en
dc.identifier.citation 26 Jul 2019. BioRxiv. 36 pages
dc.description.abstract Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. Both lower motor neuron loss and the deposition of phosphorylated TDP-43 inclusions display regional patterning along the spinal cord. The blood-spinal cord barrier (BSCB) ordinarily restricts entry into the spinal cord parenchyma of blood components that are neurotoxic, but in ALS there is evidence for barrier breakdown. Here we sought to examine whether BSCB breakdown, motor neuron loss, and TDP-43 proteinopathy display the same regional patterning across and along the spinal cord. Methods We measured cerebrospinal fluid (CSF) hemoglobin in living ALS patients (n=87 controls, n=236 ALS) as a potential biomarker of BSCB and blood-brain barrier leakage. We then immunostained cervical, thoracic, and lumbar post mortem spinal cord tissue (n=5 controls, n=13 ALS) and employed semi-automated imaging and analysis to quantify and map lower motor neuron loss and phosphorylated TDP-43 inclusion load against hemoglobin leakage. Results Motor neuron loss and TDP-43 proteinopathy were seen at all three levels of the ALS spinal cord, with most abundant TDP-43 deposition in the ventral grey (lamina IX) of the cervical and lumbar cord. In contrast, hemoglobin leakage was observed along the ALS spinal cord axis but was most severe in the dorsal grey and white matter in the thoracic spinal cord. Conclusions Our data show that leakage of the blood-spinal cord barrier occurs during life but at end-stage its distribution is independent from the major motor neuron pathology and is unlikely to be a major contributor to pathogenesis in ALS. en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS en
dc.type Journal Article en
dc.identifier.doi 10.1101/704270 en 2020-09-08T04:43:35Z en
dc.rights.holder Copyright: The author en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Preprint en
pubs.elements-id 778511 en

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