TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy

Topic: Brain proteins, microglia and lab models

Epidemiological evidence suggests that the incidence of amyotrophic lateral sclerosis is increased in association with head injury. Repetitive head injury is also associated with the development of chronic traumatic encephalopathy (CTE), a tauopathy characterized by neurofibrillary tangles throughout the brain in the relative absence of β-amyloid deposits. We examined 12 cases of CTE and, in 10, found a widespread TAR DNA-binding protein of approximately 43kd (TDP-43) proteinopathy affecting the frontal and temporal cortices, medial temporal lobe, basal ganglia, diencephalon, and brainstem. Three athletes with CTE also developed a progressive motor neuron disease with profound weakness, atrophy, spasticity, and fasciculations several years before death. In these 3 cases, there were abundant TDP-43-positive inclusions and neurites in the spinal cord in addition to tau neurofibrillary changes, motor neuron loss, and corticospinal tract degeneration. The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected. Akin to frontotemporal lobar degeneration with TDP-43 inclusions, in some individuals with CTE, the TDP-43 proteinopathy extends to involve the spinal cord and is associated with motor neuron disease. This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease.

@article{mckee2010-20720505,
  author  = {McKee, A. C. and Gavett, B. E. and Stern, R. A. and Nowinski, C. J. and Cantu, R. C. and Kowall, N. W. and Perl, D. P. and Hedley-Whyte, E. T. and others},
  title   = {{TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy}},
  journal = {Journal of neuropathology and experimental neurology},
  year    = {2010},
  doi     = {10.1097/nen.0b013e3181ee7d85},
  pmid    = {20720505},
  url     = {https://doi.org/10.1097/nen.0b013e3181ee7d85}
}

Key findings

• Epidemiological evidence suggests that the incidence of amyotrophic lateral sclerosis is increased in association with head injury.
• Repetitive head injury is also associated with the development of chronic traumatic encephalopathy (CTE), a tauopathy characterized by neurofibrillary tangles throughout the brain in the relative absence of β-amyloid deposits.
• The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected.
• Akin to frontotemporal lobar degeneration with TDP-43 inclusions, in some individuals with CTE, the TDP-43 proteinopathy extends to involve the spinal cord and is associated with motor neuron disease.
• This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease.

Why it matters

In 12 cases of chronic traumatic encephalopathy, 10 had widespread TDP-43 proteinopathy, and three also developed a progressive motor neuron disease with TDP-43 inclusions in the spinal cord. This is pathological evidence linking repetitive head injury to TDP-43 disease and does not test a treatment.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1097/nen.0b013e3181ee7d85
• PubMed: 20720505
• Original source →
• Free full text: Journal of Neuropathology & Experimental Neurology →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

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• Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model Brain : a journal of neurology · 2018-02-01 · usefulness score 58/100 · TREM2 and immune genetics
• Mild traumatic brain injury: a risk factor for neurodegeneration Alzheimer's research & therapy · 2010-06-25 · usefulness score 56/100 · Prevention and risk

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