Fast progression in amyotrophic lateral sclerosis is associated with greater tdp-43 burden in spinal cord

Sahara J. Cathcart, Stanley H. Appel, Leif E. Peterson, Ericka P. Greene, Suzanne Z. Powell, Anithachristy S. Arumanayagam, Andreana L. Rivera, Matthew D. Cykowski

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Upper and lower motor neuron pathologies are critical to the autopsy diagnosis of amyotrophic lateral sclerosis (ALS). Further investigation is needed to determine how the relative burden of these pathologies affects the disease course. We performed a blinded, retrospective study of 38 ALS patients, examining the association between pathologic measures in motor cortex, hypoglossal nucleus, and lumbar cord with clinical data, including progression rate and disease duration, site of symptom onset, and upper and lower motor neuron signs. The most critical finding in our study was that TAR DNA-binding protein 43 kDa (TDP-43) pathologic burden in lumbar cord and hypoglossal nucleus was significantly associated with a faster progression rate with reduced survival (p < 0.02). There was no correlation between TDP-43 burden and the severity of cell loss, and no significant clinical associations were identified for motor cortex TDP-43 burden or severity of cell loss in motor cortex. C9orf72 expansion was associated with shorter disease duration (p < 0.001) but was not significantly associated with pathologic measures in these regions. The association between lower motor neuron TDP-43 burden and fast progression with reduced survival in ALS provides further support for the study of TDP-43 as a disease biomarker.

Original languageEnglish (US)
Pages (from-to)754-763
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Issue number8
StatePublished - Aug 1 2021


  • Amyotrophic lateral sclerosis
  • Lower motor neuron
  • Motor cortex
  • Progression rate
  • Spinal cord
  • TAR DNA-binding protein 43 kDa (TDP-43)
  • Upper motor neuron
  • Motor Cortex/metabolism
  • Humans
  • Middle Aged
  • Spinal Cord/metabolism
  • Male
  • DNA-Binding Proteins/metabolism
  • Disease Progression
  • C9orf72 Protein/metabolism
  • Adult
  • Female
  • Aged
  • Amyotrophic Lateral Sclerosis/metabolism

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience
  • Pathology and Forensic Medicine


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