As any plumber will tell you, if you want to plug a leak, first you have to find it. Leaks in the thousands of blood vessels that infiltrate the central nervous system are no exception. Researchers have long suspected that a breached blood-brain barrier increases the risk for neuronal damage and cognitive decline, but where that breach first occurs has been a mystery. Now, in the January 21 Neuron, researchers led by Berislav Zlokovic at the University of Southern California, Los Angeles, report that in older adults the blood-brain barrier first becomes compromised in subdivisions of the hippocampus. In people with mild cognitive impairment, those leaks are worse. The findings suggest that damage to the barrier puts people at risk of future dementia.
Working with colleagues at USC, and other institutions in the LA area, Zlokovic used dynamic contrast-enhanced MRI to measure the permeability of the blood-brain barrier. Oncologists pioneered DCE-MRI to spot blood vessels invading soft tumors. The method relies on a contrast agent that normally cannot pass through capillaries, and it has high spatial resolution.
First author Axel Montagne and colleagues imaged 12 different regions of the brain in cognitively normal young and old adults, and in older adults with mild cognitive impairment. They found that the BBB became more permeable as people aged, and even leakier in those with MCI. The leakage was not generalized, but started specifically in the hippocampus. It correlated with damage to pericytes, specialized cells that seal blood vessels in the brain and protect neurons from toxins in the plasma, and occurred in the absence of changes to cerebrospinal fluid levels of Aβ or tau. Zlokovic will discuss the findings in an Alzforum webinar on February 17.—Tom Fagan
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- Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z, Toga AW, Jacobs RE, Liu CY, Amezcua L, Harrington MG, Chui HC, Law M, Zlokovic BV. Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015 Jan 21;85(2):296-302. PubMed.