Researchers have long speculated that leakages in the blood-brain barrier (BBB) are at least in part to blame for the increased neuronal damage and cognitive decline in the elderly, but no one was able to definitively show where those breaches first appear.
Now, a group of researchers led by Berislav Zlokovic, a neuroscientist from the University of Southern California, Los Angeles report that the first site this happens at is located in the hippocampus – an area of the brain largely responsible for both short- and long-term memory.
As the breakdown of the BBB becomes chronic, blood-derived neurotoxic proteins start to accumulate in the central nervous system, causing progressive neurodegeneration via direct neuronal toxicity, oxidant stress and/or detachment of neurons from their supporting extracellular matrix.
Leakages in the hippocampal area have already been implicated in age-related memory problems, but this study is the first to demonstrate this effect by performing MRI scans on living people.
Zlokovic and his team recruited 64 adults (aged 23 to 91) who were either completely healthy or had mild cognitive impairment and scanned their brains using an advanced dynamic contrast-enhanced MRI (DCE-MRI) – a technique invented by oncologists to spot blood vessels invading soft tumours. This method relies on a contrast agent called gadolinium that normally cannot pass the BBB.
Scanning 12 different regions of the brain, Zlokovic et. al. found that the older the brain, the more leakages it has. But rather than being generalized, these begin specifically in the hippocampus. The most permeable BBB were found in those with mild cognitive impairment. 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.
“This is a significant step in understanding how the vascular system affects the health of our brains,” said Zlokovic. “To prevent dementias, including Alzheimer’s, we may need to come up with way to reseal the blood-brain barrier and prevent the brain from being flooded with toxic chemicals in the blood. Pericytes are the gatekeepers of the blood-brain barrier and may be an important target for prevention of dementia.”
This study, no matter how intriguing, is too preliminary to draw any wide-ranging conclusions, however – it is not yet clear whether compromises in the BBB cause cognitive impairment or are the result of it.
The findings were published in the scientific journal Neuron.