Biomarkers.

Area of Science:

• Neuroscience
• Neurology
• Biomarkers

Background:

• Alzheimer Disease (AD) is the most common dementia, and Traumatic Brain Injury (TBI) increases dementia risk.
• Both AD and TBI are tauopathies, but TBI's effect on AD-like tau phosphorylation is unclear.
• Phospho-tau217 (p-tau217) is an emerging biomarker for early tau abnormality in AD.

Purpose of the Study:

• To investigate if CSF tau phosphorylation, amyloid deposition, tau aggregation, and neurodegeneration are elevated in cognitively normal individuals with a history of TBI.
• To assess the relationship between TBI severity and AD biomarkers.

Main Methods:

• Analyzed cerebrospinal fluid (CSF) p-tau measures in 242 cognitively normal individuals with TBI history.
• Quantified tau phosphorylation at T181, T205, and T217 sites using Mass Spectrometry.
• Assessed amyloid and tau burden via PET scans and estimated neurodegeneration using MRI.

Main Results:

• TBI severity significantly predicted p-tau217 levels, with the most severe TBI (loss of consciousness >30 min) showing the highest p-tau217.
• Severe TBI also predicted increased amyloid deposition, but not tau deposition or neurodegeneration.
• The association between TBI severity and p-tau217 was specific to the T217 site.

Conclusions:

• Prior severe TBI is associated with elevated amyloid deposition and selective p-tau217 in asymptomatic individuals.
• This suggests an increased vulnerability to Alzheimer Disease progression following severe TBI.
• Accelerated neurodegeneration was not observed in this cohort, indicating a potential preclinical stage.