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Related Experiment Video

Updated: Aug 26, 2025

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
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Greater tau pathology is associated with altered predictive coding.

Klevest Gjini1, Cameron Casey2, Sean Tanabe2

  • 1Department of Neurology, University of Wisconsin, Madison, WI, USA.

Brain Communications
|October 13, 2022
PubMed
Summary
This summary is machine-generated.

Altered predictive coding, indicated by reduced auditory mismatch negativity, is linked to preclinical Alzheimer's disease. Tau pathology correlates with disrupted neural signaling, suggesting potential early detection methods.

Keywords:
auditory event-related potentialsdynamic casual modellingmismatch negativitypredictive codingtau

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Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
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Area of Science:

  • Neuroscience
  • Cognitive Science
  • Medical Imaging

Background:

  • Altered predictive coding may explain reduced auditory mismatch negativity (MMN) in dementia.
  • Dementia-associated pathologies like amyloid and tau could disrupt sensory predictions, increasing reliance on observed information and altering neural signaling.
  • This study investigates the link between these pathologies and neural signaling changes.

Purpose of the Study:

  • To test the hypothesis that accumulating dementia pathologies (amyloid, tau) disrupt predictive coding, leading to altered neural signaling.
  • To investigate the relationship between tau pathology, amyloid burden, and auditory evoked responses using advanced neuroimaging and modeling techniques.
  • To explore the potential of MMN as a biomarker for preclinical Alzheimer's disease.

Main Methods:

  • Cross-sectional study involving 56 participants undergoing PET imaging (amyloid-β, tau) and high-density EEG during an oddball paradigm.
  • Dynamic causal modeling and Bayesian statistics were used to analyze neuronal architectures and effective connectivity.
  • PET scans were analyzed for amyloid-β and tau positivity using established criteria and standardized uptake value ratios.

Main Results:

  • Significantly smaller Mismatch Negativity (MMN) amplitudes were observed in the tau-positive subgroup compared to the tau-negative subgroup (P=0.028).
  • Dynamic causal modeling revealed that tau pathology is associated with increased feedforward and decreased feedback connectivity, particularly affecting superior temporal gyrus excitability.
  • These findings were consistent with tau distribution on PET scans and persisted after excluding participants with diagnosed mild cognitive impairment or dementia.

Conclusions:

  • Abnormalities in predictive coding, detectable via MMN, may indicate preclinical Alzheimer's disease.
  • The study provides a framework for understanding how progressive impairments affect sensory orientation in dementia.
  • MMN could serve as a valuable monitoring tool for developing interventions targeting interneuron dysfunction in Alzheimer's disease.