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J Neurotrauma. 2019 Aug 23. doi: 10.1089/neu.2019.6711. [Epub ahead of print]

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

Author information

1
UCSF, 8785, Medicine, 1719 Broderick St., San Francisco, California, United States, 94115; edward.goetzl@ucsf.edu.
2
San Francisco VA Medical Center, San Francisco, United States; carrie.peltz2@va.gov.
3
National Institute on Aging Intramural Research Program, 171247, Human Neuroscience Unit, 251 Bayview blvd, Baltimore, Maryland, United States, 21230; maja.mustapic@nih.gov.
4
National Institute on Aging Intramural Research Program, 171247, Laboratory of Neurosciences (LNS), 3001 S. Hanover St, NM531, Baltimore, Maryland, United States, 21225; kapogiannisd@mail.nih.gov.
5
UCSF and San Francisco VA Medical Center, Neurology, Psychiatry, and Epidemiology, San Francisco, California, United States; Kristine.Yaffe@ucsf.edu.

Abstract

To identify long-term effects of traumatic brain injury (TBI) on levels of plasma neuron-derived exosome (NDE) protein biomarkers of cognitive impairment (CI), plasmas were obtained from four groups of older veterans, who were matched for age and gender: no TBI or CI (n=42), no TBI with CI (n=19), TBI without CI (n=21) and TBI with CI (n=26). TBI was sustained 12 to 74 years before study in 75%. NDEs were enriched by sequential precipitation and anti-L1CAM antibody immunoabsorption, and extracted protein biomarkers were quantified by enzyme-linked immunosorbent assays. Chronic NDE biomarkers known to increase for three to 12 months after TBI, including cellular prion protein (PrPc), synaptogyrin-3, P-T181-tau, P-S396-tau, Aβ42 and IL-6 were elevated significantly in subjects who had TBI and CI compared to controls with TBI but no CI. Chronic NDE biomarker levels in subjects without TBI showed significantly higher levels of PrPc, synaptogyrin-3, P-T181-tau and Aβ42, but not P-S396-tau and IL-6, in those with CI compared to controls without CI. The acute NDE biomarkers claudin-5, annexin VII and aquaporin-4 were not increased in either group with CI. The NDE biomarkers P-S396-tau and IL-6, that are increased distinctively with CI after TBI, may prove useful in evaluating CI in older patients. Aβ42 and P-tau species, as well as their respective putative receptors, PrPc and synaptogyrin-3, remain elevated for decades after TBI, and may mediate TBI-associated CI and be useful targets for development of drugs.

KEYWORDS:

ADULT BRAIN INJURY; BIOMARKERS; NEURODEGENERATIVE DISORDERS

PMID:
31441374
DOI:
10.1089/neu.2019.6711

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