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Basic Science and Pathogenesis.

Wanyong Shin1, James B Leverenz1,2, Mark J Lowe1

  • 1Cleveland Clinic, Cleveland, OH, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
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Summary
This summary is machine-generated.

Alzheimer's Disease (AD) is linked to increased blood-brain barrier (BBB) permeability in specific brain regions, correlating with cognitive decline severity. These BBB changes are more pronounced in AD dementia than mild cognitive impairment (MCI).

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Area of Science:

  • Neuroimaging
  • Neuroscience
  • Biomarkers

Background:

  • Alzheimer's Disease (AD) pathophysiology involves inflammation and neurovascular dysfunction.
  • Understanding blood-brain barrier (BBB) disruption is crucial for AD research.
  • Brain region-specific BBB changes in distinct AD clinical stages require further characterization.

Purpose of the Study:

  • To investigate brain region-specific alterations in BBB permeability across different clinical stages of AD.
  • To compare BBB permeability in AD dementia, mild cognitive impairment (MCI), and healthy controls (HC).

Main Methods:

  • Dynamic contrast-enhanced (DCE) MRI at 3T was used to assess BBB permeability (Ktrans).
  • 41 participants (6 AD dementia, 16 MCI, 19 HC) were analyzed using the Patlak model.
  • Ktrans values were calculated in subcortical gray matter and lobar regions.

Main Results:

  • Significantly higher Ktrans values (indicating increased BBB permeability) were observed in the thalamus, caudate, putamen, amygdala, hippocampus, and occipital regions in AD patients compared to HC.
  • A significant negative correlation was found between Ktrans values and Montreal Cognitive Assessment (MOCA) scores, suggesting a link between BBB permeability and cognitive function.

Conclusions:

  • Increased BBB permeability in specific subcortical and cortical gray matter regions is more prominent in AD dementia than MCI.
  • These BBB alterations are significantly different between AD patients and HC.
  • The degree of BBB disruption linearly tracks the severity of cognitive decline in AD.