Mechanisms of Cortical Excitability Changes in Frontotemporal Degeneration Onset
Abstract
Head injuries, including combat-related trauma like TBI, increase lifetime risk of acquired dementias, including Frontotemporal Degeneration (FTD). A major pathological mechanism of dementias like FTD is misfolding and aggregation of Tau isoforms. But there is not yet an effective treatment targeting Tau aggregation that addresses clinical symptoms or slows disease progression. Early pathological changes include hyperexcitability and increased seizure incidence, which precede substantial Tau aggregation and FTD diagnosis. There is a significant knowledge gap about how changes in circuits lead to hyperexcitability. Understanding the pathogenesis in the cortical circuit might help identify potential therapeutic targets to treat or slow the progression of FTD. We hypothesize that pre-tangle mutant Tau induces circuit changes, resulting in weakened inhibition or increased neuronal excitability in specific circuit components.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2023
- Accession Number
- AD1212999
Entities
People
- Bryan M Hooks
- Roman Goz
Organizations
- University of Pittsburgh