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Neuron-Derived Plasma Exosome Proteins after Remote Traumatic Brain Injury.

Edward J Goetzl1, Carrie B Peltz2,3, Maja Mustapic4

  • 1Department of Medicine, University of California, San Francisco, San Francisco, California.

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|August 24, 2019
PubMed
Summary
This summary is machine-generated.

Long-term traumatic brain injury (TBI) elevates specific neuron-derived exosome (NDE) biomarkers, such as P-S396-tau and IL-6, indicating cognitive impairment (CI). These biomarkers, along with Aβ42 and P-tau species, may help evaluate CI after TBI.

Keywords:
amyloidbiomarkersphospho-tauprion cellular proteinproteinopathic neurodegenerationsynaptogyrin-3

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Area of Science:

  • Neuroscience
  • Biomarkers
  • Traumatic Brain Injury

Background:

  • Traumatic brain injury (TBI) can lead to long-term cognitive impairment (CI).
  • Plasma neuron-derived exosome (NDE) protein biomarkers are being investigated for their role in TBI-associated CI.
  • Understanding chronic TBI effects on NDE biomarkers is crucial for diagnosis and treatment.

Purpose of the Study:

  • To identify long-term effects of TBI on plasma NDE protein biomarkers associated with CI.
  • To evaluate the potential of specific NDE biomarkers for assessing CI in older veterans with a history of TBI.

Main Methods:

  • Plasma samples were collected from four groups of older veterans: no TBI/CI, no TBI/CI, TBI/no CI, and TBI/CI.
  • NDE proteins were enriched using sequential precipitation and immunoabsorption.
  • Quantification of biomarkers including PrPc, synaptogyrin-3, P-T181-tau, P-S396-tau, Aβ42, and IL-6 was performed using ELISAs.

Main Results:

  • Elevated levels of chronic NDE biomarkers (PrPc, synaptogyrin-3, P-T181-tau, P-S396-tau, Aβ42, IL-6) were observed in subjects with TBI and CI compared to those with TBI but no CI.
  • In subjects without TBI, CI was associated with higher levels of PrPc, synaptogyrin-3, P-T181-tau, and Aβ42.
  • Acute NDE biomarkers (claudin-5, annexin VII, aquaporin-4) were not elevated in groups with CI.

Conclusions:

  • NDE biomarkers P-S396-tau and IL-6 are distinctively increased with CI after TBI and may aid in evaluating CI in older patients.
  • Aβ42 and P-tau species, along with their receptors PrPc and synaptogyrin-3, remain elevated for decades post-TBI.
  • These long-term elevated biomarkers may mediate TBI-associated CI and represent potential therapeutic targets.