Amyotrophic lateral sclerosis (ALS) is a progressive motor disorder, and many patients also show non-motor symptoms including executive, behavioural and language dysfunction. A new study demonstrates a robust relationship between progression of these non-motor symptoms and declining motor disease in patients with ALS, providing important insights into mechanisms of ALS pathogenesis.
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References
Burrell, J. R. et al. The frontotemporal dementia-motor neuron disease continuum. Lancet 388, 919–931 (2016).
Brettschneider, J. et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann. Neurol. 74, 20–38 (2013).
Goldstein, L. H. & Abrahams, S. Changes in cognition and behaviour in amyotrophic lateral sclerosis: nature of impairment and implications for assessment. Lancet Neurol. 12, 368–380 (2013).
Menke, R. A. L. et al. Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis. Brain 137, 2546–2555 (2014).
Crockford, C. et al. ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS. Neurology 91, e1370–e1380 (2018).
Placek, K. et al. UNC13A polymorphism contributes to frontotemporal disease in sporadic amyotrophic lateral sclerosis. Neurobiol. Aging 73, 190–199 (2018).
McMillan, C. T. et al. C9orf72 promoter hypermethylation is neuroprotective: neuroimaging and neuropathologic evidence. Neurology 84, 1622–1630 (2015).
Covell, D. J. et al. Novel conformation-selective alpha-synuclein antibodies raised against different in vitro fibril forms show distinct patterns of Lewy pathology in Parkinson’s disease. Neuropathol. Appl. Neurobiol. 43, 604–620 (2017).
Brettschneider, J. et al. Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat. Rev. Neurosci. 16, 109–120 (2015).
Schulthess, I. et al. Functional connectivity changes resemble patterns of pTDP-43 pathology in amyotrophic lateral sclerosis. Sci. Rep. 6, 38391 (2016).
Acknowledgements
This work was supported in part by grants from NIH (AG052943, AG054519, AG017586), the Wyncote Foundation and anonymous philanthropic support. The author receives financial support for research projects from Biogen and Avid, support in kind from Avid and Piramal, financial support for consultation from Biogen and Bracco, and financial support as an editor for Neurology. None of these sources of support constitute a conflict of interest with this work.
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Grossman, M. Amyotrophic lateral sclerosis — a multisystem neurodegenerative disorder. Nat Rev Neurol 15, 5–6 (2019). https://doi.org/10.1038/s41582-018-0103-y
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DOI: https://doi.org/10.1038/s41582-018-0103-y
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