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Basic Science and Pathogenesis.

Gawon Cho1, Ryan S O'Dell1,2, Xiao Liu3

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In preclinical Alzheimer's disease, stronger gray matter BOLD-CSF coupling was unexpectedly linked to higher levels of tau and amyloid-beta. This suggests sleep state influences brain fluid dynamics and should be considered in imaging studies.

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Area of Science:

  • Neuroimaging
  • Neurodegenerative Diseases
  • Brain Fluid Dynamics

Background:

  • Reduced glymphatic clearance is implicated in Alzheimer's disease (AD).
  • Glymphatic clearance relies on cerebrospinal fluid (CSF) flow, which is temporally coupled to brain activity.
  • The association between this coupling and AD biomarkers in preclinical stages needs investigation.

Purpose of the Study:

  • To investigate the relationship between gray matter BOLD-CSF coupling and core Alzheimer's disease (AD) biomarkers (amyloid-beta, tau, neurodegeneration) in cognitively normal individuals.
  • To explore potential alterations in brain fluid dynamics in preclinical AD.

Main Methods:

  • Utilized resting-state fMRI, [11C]PiB, [18F]MK-6240, and [11C]UCB-J PET scans in 21 cognitively normal participants.
  • Quantified gray matter BOLD-CSF coupling via cross-correlation analysis.
  • Assessed associations with global amyloid-beta, regional tau deposition (Braak stages), and global synaptic density.

Main Results:

  • Gray matter BOLD-CSF coupling showed a negative association with tau in the entorhinal cortex, hippocampus, and amygdala.
  • A weak negative association was observed between coupling and global cortical amyloid-beta and tau in other regions.
  • No significant association was found with global synaptic density.

Conclusions:

  • Contrary to hypotheses, higher amyloid-beta and tau levels were associated with stronger gray matter BOLD-CSF anti-correlation.
  • Sleep state may influence glymphatic function and brain fluid transport, impacting imaging findings.
  • Future research should account for sleep-wake states in studies of brain fluid dynamics and AD.