Neuropathology and Immune Biomarker Discovery in a Rat Model of Alzheimer's Disease, TgF344-AD, with Single or Repetitive Traumatic Brain Injury
Abstract
Purpose: The major goals of this project were to develop better models to investigate mechanisms by which traumatic brain injury (TBI) is a risk factor for developing Alzheimer's disease (AD) and related neurodegenerative diseases, including chronic traumatic encephalopathy (CTE). To accomplish these goals, we used wild-type (WT) F344 control and the transgenic (Tg) AD rat model, Tg-F344-AD, to conduct and contrast two paradigms of closed-head controlled cortical impact TBI (i.e. 1X-CCI and 2X-CCI), and one paradigm of repetitive moderate blast TBI (i.e. rmTBI), after which cohorts of varying ages post-injury were studied for neuropathology and immune system changes in the periphery and CNS to determine their role in AD pathogenesis.Scope: The study was limited to developing and characterizing these new TBI-AD models, and did not incorporate treatments or translational efforts for human clinical settings.Major Findings: The 1X- and 2X-CCI experiments in 6-month-old animals did not induce detectable AD pathologies in the brain or in pathology-associated plasma biomarker profiles. However, experiments in 12-month-old TgF344-AD rats revealed that 2X-CCI induced maturation of diffuse plaques into -sheet positive dense-cored plaques, coincident with induction of astrogliosis and tauopathy in the vicinity of the impact site, of which occurred about four months earlier than expected from previous characterizations of the TgF344-AD model (Cohen et al., 2013). These data indicate that TBI may not induce detectable ADpathologies, but that it may exacerbate or accelerate existing AD pathology, thus providing evidence of mechanisms that may underlie TBIs risk for the onset of clinical presentation of AD and related dementias (ADRD).
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2021
- Accession Number
- AD1213963
Entities
People
- Huntington Potter
Organizations
- University of Colorado Boulder