Leaky Blood-Brain Barrier Linked to Alzheimer’s Disease

Global, diffusely distributed blood-brain barrier (BBB) leakage in patients with early Alzheimer’s disease (AD) suggests that a compromised BBB is part of the early pathology of AD and might be part of a cascade of pathologic events that eventually lead to cognitive decline, according to new Radiology research.

Harm J. van de Haar, MSc, of Maastricht University Medical Center in Maastricht, the Netherlands, and colleagues found that the BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter and cortex. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material–enhanced MRI sequence with dual time resolution for 25 minutes.

Patients had a significantly higher volume fraction of the leaking brain tissue in the GM, normal-appearing white matter, deep gray matter and cortex. When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter and cortex.

“We found an increased BBB leakage rate in the gray matter of patients with early AD. By also showing very subtle BBB impairment in the white matter, leakage volume proved to be even more sensitive to the differences in BBB leakage than was the leak­age rate,” the authors write.

A, Axial fluid-attenuated inversion recovery image in a 68-year-old man with, B, corresponding blood-brain barrier leakage rate (Ki) maps superimposed
Figure 1. A, Axial fluid-attenuated inversion recovery image in a 68-year-old man with, B, corresponding blood-brain barrier leakage rate (Ki) maps superimposed. Leakage rate values appear diffusely distributed on both images, with some periventricular hot spots. Leakage manifests in normal-appearing white matter, white matter hyperintensities and gray matter. Voxels with low signal-to-noise ratio in MRI signal intensity were removed, and leakage rate map was masked to cerebrum.
A, Axial fluid-attenuated inversion recovery image in an 80-year-old woman healthy control subject with, B, corresponding blood-brain barrier leakage rate (Ki) maps superimposed
Figure 2. A, Axial fluid-attenuated inversion recovery image in an 80-year-old woman healthy control subject with, B, corresponding blood-brain barrier leakage rate (Ki) maps superimposed. Voxels with low signal-to-noise ratio in MRI signal intensity were removed, and leakage rate map was masked to cerebrum.

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