Blood-brain barrier breakdown in the aging human hippocampus

Area of Science:

• Neuroscience
• Gerontology
• Radiology

Background:

• The blood-brain barrier (BBB) protects the brain but its breakdown is implicated in Alzheimer's disease (AD).
• The precise timing of BBB dysfunction during aging and early AD remains unclear.
• The hippocampus is crucial for memory and is affected early in AD.

Purpose of the Study:

• To investigate the age-dependent breakdown of the BBB in the living human brain.
• To determine if BBB permeability changes correlate with cognitive status and pericyte injury.

Main Methods:

• Utilized advanced dynamic contrast-enhanced MRI (DCE-MRI) for high-resolution, regional BBB permeability quantification.
• Analyzed cerebrospinal fluid (CSF) for markers of BBB-associated pericyte injury.
• Correlated BBB permeability with age and cognitive status (mild cognitive impairment).

Main Results:

• Demonstrated an age-dependent increase in BBB permeability, particularly in the hippocampus.
• Observed worsening BBB breakdown in hippocampal subregions (CA1, dentate gyrus) with mild cognitive impairment.
• Found correlations between hippocampal BBB breakdown and pericyte injury markers in CSF.

Conclusions:

• BBB breakdown is an early event in the aging brain, originating in the hippocampus.
• Hippocampal BBB dysfunction may contribute to cognitive decline and Alzheimer's disease progression.
• DCE-MRI is a valuable tool for assessing BBB integrity in vivo.