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Alzheimer's Imaging Consortium.

Lawrence P Binding1, Mihaela Croitor1, Christopher S Parker1

  • 1UCL Hawkes Institute and Department of Computer Science, University College London, London, UK.

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Summary
This summary is machine-generated.

Alzheimer's disease (AD) often involves mixed pathologies, making diagnosis challenging. New software, Additional Pathology Inference (AddiPath), can now distinguish tau deposition from other pathologies, improving diagnostic accuracy.

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Area of Science:

  • Neuroscience
  • Biomarker Discovery
  • Medical Imaging

Background:

  • Alzheimer's disease (AD) frequently presents with mixed pathologies, complicating in vivo diagnosis due to limited biomarkers for non-tau pathologies.
  • Cortical thickness (CT) atrophy is influenced by both tau deposition and other pathologies like TDP-43.
  • Existing tau-PET biomarkers can help differentiate these contributions.

Purpose of the Study:

  • To introduce Additional Pathology Inference (AddiPath) software for identifying disease biomarker changes beyond primary tau pathology.
  • To apply AddiPath to tau-PET data to detect cortical thickness (CT) changes not attributable to tau deposition.

Main Methods:

  • Analysis of paired tau-PET and CT data from 444 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects.
  • Utilized Subtype and Stage Inference (SuStaIn) on tau-PET to identify tau pathology subtypes.
  • Applied AddiPath to quantify contributions of tau and additional pathologies to regional CT values, estimating progression patterns.

Main Results:

  • SuStaIn identified distinct tau deposition subtypes (posterior, limbic, cortical).
  • AddiPath revealed an independent pathology progression pattern originating in the entorhinal cortex and spreading across the brain.
  • 84 participants showed evidence of additional pathology; increased AddiPath stages correlated with poorer cognitive function (memory, language, executive function) and were independent of tau load.

Conclusions:

  • AddiPath effectively disentangles additional pathology contributions from primary tau pathology in Alzheimer's disease.
  • Uncovered CT changes not explained by tau, potentially indicating TDP-43 deposition, particularly in the limbic lobe.
  • This method holds promise for enhancing clinical trial recruitment and patient stratification in AD research.