Targeting Toxic Oligomeric Protein Variants Generated After Traumatic Brain Injury to Decrease Risk of AD
Abstract
We analyzed brain tissue from a wild-type traumatic brain injury mouse model for presence of specific Alzheimers disease and relateddementia (ADRD) protein variant pathology. We determined the levels of 7 different ADRD related protein variants (2 beta-amyloid variants,2 tau variants, 1 TDP-43 variant and 2 a-syn variants) in 10 different brain regions as a function of time following TBI. All protein variantlevels were elevated shortly after injury even in the sham mice due to craniotomy necessary for the fluid percussion injury model. In generalthere was a short term increase in protein variant levels near the site of injury an craniotomy and a short term deficit in behavioral outcomeswhich resolved by 14 days after injury. However individual mice showed residual long term behavioral deficits and presence of toxic proteinvariants. We correlated the levels of different protein variants with behavioral outcomes for each mouse and found statistically significantcorrelations between long term accumulation of a specific oligomeric beta-amyloid variant and long term cognitive deficit and between aspecific oligomeric tau variant and emotional disruption. Additional studies to confirm these results in a second TBI model using a milder TBIwith additional co-stressors are underway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1186898
Entities
People
- Michael R Sierks
Organizations
- Arizona State University