An Investigation of Immune Biology and Alzheimers Disease-Related Biomarkers in Asymptomatic, Late-Life Mild TBI
Abstract
The development of symptomatic Alzheimer’s disease (AD) in older adults is a protracted and heterogeneous process that may be exacerbated or influenced by environmental risk factors. Recent evidence suggests that mild traumatic brain injury (mTBI) may have differential effects on clinical outcomes when sustained in late life relative to early life and may not only accelerate the aging process but also impact immune cascades and AD pathogenesis. Despite considerable interest in the biological connections between aging, mTBI, and AD, there is a dearth of prospective research on the pathophysiological processes that may underlie these associations. In order to develop preventative or acute therapies that minimize the impact of mTBI on negative aging trajectories, it is important to disentangle the relative contributions of mTBI, immune dysregulation, and AD-related pathology on longitudinal outcomes in older adults. We propose to conduct a two-timepoint study and prospectively analyze the associations between mTBI, immune biomarkers, AD-related pathology, and cognitive and neuroanatomical outcomes in asymptomatic aging adults (i.e., no current cognitive complaints) with either a history of recent mTBI or with no recent history of mTBI. We plan to examine the following aims: (1) We will examine the association between recent mTBI, immune dysregulation, and markers of AD pathology and neuronal integrity over time in asymptomatic older adults. (2) We will evaluate the association between proximal mTBI and longitudinal structural brain changes and longitudinal cognitive changes in asymptomatic older adults. We will accomplish our goals by leveraging our existing cohort of asymptomatic older adults (AOA; n = 50) from the Rocky Mountain Alzheimer’s Disease Center and will recruit an additional cohort of asymptomatic older adults with a proximal history of confirmed mTBI within the past 5 years (AOA-mTBI; n = 75) for a total of 125 older adults. We will conduct evaluations at baseline and at a 12-month follow-up visit and will assess inflammatory markers in circulating plasma, a marker of neuronal degeneration (i.e., neurofilament light chain), and markers of AD-related pathology in neuronal-derived vesicles. Our proposed study will provide prospective information regarding the relationship between mTBI, immune dysregulation, and AD-related biomarkers in older adults using innovative, multi-modal biomarkers, and will in turn serve as a platform for future studies to disentangle the pathophysiological roles of mTBI on long-term aging outcomes.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910520
Entities
People
- Brianne Bettcher
Organizations
- United States Army
- University of Colorado Denver