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Basic Science and Pathogenesis.

Zezong Gu1,2, Marcus Jackson2,3, Tamanna Mony2,4

  • 1University of Missouri, Columbia, MO, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary
This summary is machine-generated.

Mild traumatic brain injury (mTBI) accelerates Alzheimer's Disease and Related Dementias (ADRDs) risk. This study identified molecular signatures linking Tau protein interactions and mTBI to neurodegeneration, enabling early intervention for ADRDs.

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Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Traumatic brain injury (TBI), particularly mild TBI (mTBI), is linked to an increased risk of Alzheimer's Disease and Related Dementias (ADRDs).
  • The progression from TBI to tauopathy and ADRDs is complex and not fully understood.
  • Identifying early biomarkers and risk factors is crucial for intervention.

Purpose of the Study:

  • To identify gene-risk combinations and the timing of mTBI that alter biomarkers for ADRDs.
  • To understand how mTBI influences tau pathology and neurodegeneration.
  • To enable early intervention strategies for ADRDs post-TBI.

Main Methods:

  • Utilized human wild-type Tau/CamKII bitransgenic (rT1) mice subjected to repetitive mild TBI (rmTBI) via open-field blasts (OFB) or sham controls.
  • Conducted high-resolution proteomics and phospho-proteomics on brain tissues.
  • Employed AI-informed phenomic analysis integrating mouse proteomic data with human ADRD cohorts.

Main Results:

  • Identified co-expression subnetworks correlating with PTSD-like behaviors in mice post-rmTBI.
  • AI analysis revealed overlapping molecular networks in mouse and human studies differentiating ADRD conditions.
  • Key proteins involved in synaptic function and metabolism showed differential expression due to tau transgene and TBI interactions, accelerating ADRD trajectory.

Conclusions:

  • Unveiled converging molecular signatures predicting ADRD development post-TBI.
  • Demonstrated a link between Tau-TBI interaction, neuropsychiatric impairments, and neurodegeneration.
  • Provided insights into the complex etiology of ADRDs following TBI.