Editors' ChoiceAlzheimer's Disease

Leaky blood-brain barriers and memory loss

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Science Translational Medicine  04 Feb 2015:
Vol. 7, Issue 273, pp. 273ec22
DOI: 10.1126/scitranslmed.aaa5560

The blood-brain barrier (BBB) protects neurons from harmful proteins produced by blood. Breakdown of the BBB has been thought to play a role in Alzheimer’s disease. This theory is largely based on post-mortem studies of Alzheimer’s patients, which demonstrated BBB damage and accumulation of blood-derived proteins in the hippocampus, the area of the brain crucial for memory. However, it is unclear whether BBB permeability occurs before or after the onset of Alzheimer’s disease.

Montagne et al. used dynamic MRI in subjects with no or mild cognitive impairment to quantify BBB breakdown. They found that BBB permeability in the hippocampus increased linearly with age and was most severe in subjects with mild cognitive impairment. The degree of BBB breakdown detected by MRI correlated to cerebral spinal fluid biomarkers of BBB damage and permeability.

This research sheds new light on the pathophysiology of early development of Alzheimer’s disease and identifies BBB permeability as a potential therapeutic target.

A. Montagne et al., Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85, 296–302 (2015). [Abstract]

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