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Alzheimer's Imaging Consortium.

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Summary
This summary is machine-generated.

Brain network structure influences Alzheimer's Disease (AD) progression. Efficient communication from tau pathology epicenters to connector hubs amplifies amyloid's effect on tau spread and cognitive decline in AD patients.

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Area of Science:

  • Neuroscience
  • Medical Imaging
  • Network Science

Background:

  • Tau accumulation is a key driver of neurodegeneration and cognitive decline in Alzheimer's Disease (AD).
  • Preclinical models suggest tau pathology spreads transsynaptically between connected neurons.
  • This study investigates how brain network topology influences tau spreading dynamics in human AD.

Purpose of the Study:

  • To determine if functional brain network hubs accelerate tau spread in AD.
  • To test the hypothesis that communication efficiency from tau epicenters to connector hubs, versus local hubs, accelerates tau accumulation and cognitive decline.

Main Methods:

  • Analysis of longitudinal tau/amyloid-PET and cognitive data from ADNI/A4 cohorts (n=325/220).
  • Modeling connectional efficiency from subject-level tau epicenters to connector/local hubs using structural and functional connectivity templates.
  • Using robust regression to test the impact of hub communication on tau accumulation, cognitive decline, and tau dissemination.

Main Results:

  • Higher baseline amyloid-PET's effect on faster global tau-PET increase was moderated by communication efficiency to connector hubs (ADNI/A4: β=0.31/0.40, p<0.001/0.03).
  • Stronger epicenter communication to connector hubs amplified amyloid's effect on tau accumulation rates.
  • This interaction also predicted faster cognitive decline (ADNI/A4: β=-0.49/-0.34, p<0.001/0.04) and greater tau dissemination across networks (ADNI/A4: β=0.6/0.36, p<0.001/0.04).

Conclusions:

  • Brain network topology significantly shapes tau accumulation rates and cognitive trajectories in AD.
  • Enhanced communication between tau epicenters and connector hubs amplifies amyloid-related tau accumulation.
  • Brain network architecture plays a critical role in modulating tau aggregation and AD progression.