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Plamena P Powla1, Theyaneshwaran Jayaprakash2, Connor Lee Cornelison2

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This study reveals that tau protein spreads differently across brain networks in Alzheimer's disease, with higher diffusion in the frontoparietal network (FPN) and default mode network (DMN). Tau diffusion is also faster in females compared to males, particularly in the limbic system network (LSN).

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Area of Science:

  • Neuroscience
  • Biomedical Engineering
  • Medical Imaging

Background:

  • Alzheimer's disease (AD) is marked by tau tangles spreading across the brain, causing cognitive decline.
  • Cortical regions with low tau levels are functionally connected to high-tau regions, suggesting network-specific diffusion patterns.
  • Early AD shows tau-related hypoconnectivity in the default mode network (DMN), indicating differential spread across functional networks.

Purpose of the Study:

  • To investigate tau diffusion across functionally connected brain networks.
  • To determine if tau diffusion differs across distinct functional networks.
  • To examine sex-based differences in tau diffusion patterns.

Main Methods:

  • Utilized multilevel network diffusion models adapted from social influence models.
  • Analyzed data from 321 subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI 3).
  • Compared tau diffusion across functional networks (DMN, LSN, FPN, DAN, SMN, VISN, VAN) and investigated sex interactions.

Main Results:

  • Significant diffusion differences were observed across dorsal attention (DAN), limbic system (LSN), sensorimotor (SMN), ventral attention (VAN), and visual (VISN) networks compared to the DMN.
  • The frontoparietal network (FPN) and default mode network (DMN) exhibited the highest rates of tau diffusion.
  • Females showed stronger tau diffusion in the LSN, suggesting faster spread in women than men.

Conclusions:

  • Tau diffusion is highest in the FPN and DMN, aligning with previous findings on network-specific glucose metabolism in AD.
  • Increased tau diffusion in the LSN of females corroborates prior research on greater tau distribution in women's limbic regions.
  • The study highlights network-specific and sex-differentiated tau diffusion patterns in Alzheimer's disease.