TDP-43 pathology and neuronal loss in amyotrophic lateral sclerosis spinal cord View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-06-12

AUTHORS

Johannes Brettschneider, Kimihito Arai, Kelly Del Tredici, Jon B. Toledo, John L. Robinson, Edward B. Lee, Satoshi Kuwabara, Kazumoto Shibuya, David J. Irwin, Lubin Fang, Vivianna M. Van Deerlin, Lauren Elman, Leo McCluskey, Albert C. Ludolph, Virginia M.-Y. Lee, Heiko Braak, John Q. Trojanowski

ABSTRACT

We examined the phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) inclusions as well as neuronal loss in full-length spinal cords and five selected regions of the central nervous system from 36 patients with amyotrophic lateral sclerosis (ALS) and 10 age-matched normal controls. The most severe neuronal loss and pTDP-43 lesions were seen in lamina IX motor nuclei columns 4, 6, and 8 of lower cervical segments and in columns 9–11 of lumbosacral segments. Severity of pTDP-43 pathology and neuronal loss correlated closely with gray and white matter oligodendroglial involvement and was linked to onset of disease, with severe involvement of columns 4, 6, and 8 of upper extremity onset cases and severe involvement of columns of 9, 10, and 11 in cases with lower extremity onset. Severe TDP-43 lesions and neuronal loss were observed in stage 4 cases and sometimes included Onuf’s nucleus. Notably, three cases displayed pTDP-43 aggregates in the midbrain oculomotor nucleus, which we had not seen previously even in cases with advanced (i.e., stage 4) pathology. pTDP-43 aggregates were observed in neurons of Clarke’s column in 30.6 % of cases but rarely in the intermediolateral nucleus (IML). Gray matter oligodendroglial pTDP-43 inclusions were present in areas devoid of neuronal pTDP-43 aggregates and neuronal loss. Taken together, our findings indicate that (1) the dorsolateral motor nuclei columns of the cervical and lumbosacral anterior horn may be the earliest foci of pTDP-43 pathology in the spinal cord, (2) gray matter oligodendroglial involvement is an early event in the ALS disease process that possibly heralds subsequent involvement of neurons by pTDP-43 pathology, and (3) in some very advanced cases, there is oculomotor nucleus involvement, which may constitute an additional neuropathological stage (designated here as stage 5) of pTDP-43 pathology in ALS. More... »

PAGES

423-437

References to SciGraph publications

  • 2008-10-16. Sporadic amyotrophic lateral sclerosis of long duration is associated with relatively mild TDP-43 pathology in ACTA NEUROPATHOLOGICA
  • 2012-03-18. Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansion in ACTA NEUROPATHOLOGICA
  • 2006-08-12. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry in ACTA NEUROPATHOLOGICA
  • 2012-07-11. Oligodendroglia metabolically support axons and contribute to neurodegeneration in NATURE
  • 2013-03-31. Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis in NATURE NEUROSCIENCE
  • 2012-01-07. Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p in ACTA NEUROPATHOLOGICA
  • 2010-12-15. The pathological process underlying Alzheimer’s disease in individuals under thirty in ACTA NEUROPATHOLOGICA
  • 2012-01-01. Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis in ACTA NEUROPATHOLOGICA
  • 2014-01-27. Dendritic retraction, but not atrophy, is consistent in amyotrophic lateral sclerosis-comparison between Onuf’s neurons and other sacral motor neurons- in ACTA NEUROPATHOLOGICA COMMUNICATIONS
  • 2013-11-12. Amyotrophic lateral sclerosis—a model of corticofugal axonal spread in NATURE REVIEWS NEUROLOGY
  • 2014-02-06. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases in NATURE MEDICINE
  • 1994-10. Motor neuron disease with dementia and ophthalmoplegia in JOURNAL OF NEUROLOGY
  • 2010-04-09. Amyotrophic lateral sclerosis: dash-like accumulation of phosphorylated TDP-43 in somatodendritic and axonal compartments of somatomotor neurons of the lower brainstem and spinal cord in ACTA NEUROPATHOLOGICA
  • 2007-09-05. TDP-43-immunoreactive neuronal and glial inclusions in the neostriatum in amyotrophic lateral sclerosis with and without dementia in ACTA NEUROPATHOLOGICA
  • 2014-01-10. Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD) in ACTA NEUROPATHOLOGICA
  • 2013-09-04. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases in NATURE
  • 2002-07. Defining the NG2-expressing cell of the adult CNS in BRAIN CELL BIOLOGY
  • 2011-11-30. Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration in NATURE REVIEWS NEUROSCIENCE
  • 1991-09. Neuropathological stageing of Alzheimer-related changes in ACTA NEUROPATHOLOGICA
  • 2012-09-01. Co-aggregation of RNA binding proteins in ALS spinal motor neurons: evidence of a common pathogenic mechanism in ACTA NEUROPATHOLOGICA
  • 2008-05-15. Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions in ACTA NEUROPATHOLOGICA
  • 2008-06-17. Maturation process of TDP-43-positive neuronal cytoplasmic inclusions in amyotrophic lateral sclerosis with and without dementia in ACTA NEUROPATHOLOGICA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00401-014-1299-6

    DOI

    http://dx.doi.org/10.1007/s00401-014-1299-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1017346963

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24916269


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