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Blood-brain barrier test may predict dementia

From NIH Research Matters

Cognitive impairment is when a person has problems remembering, learning, concentrating, or making decisions that affect everyday life. Millions of people in the U.S. show some sort of cognitive impairment. People with cognitive impairment are at higher risk for developing dementia, which is the loss of cognitive functioning. Alzheimer's disease is the most common dementia diagnosis.

Nurse with patient in front of MRI
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Researchers have been looking for ways to test for early signs of cognitive impairment and dementia. Early detection could open the door to strategies that prevent disease progression. Potential biomarkers include changes in the size and function of the brain and its parts, as well as levels of certain proteins seen on brain scans, in cerebrospinal fluid, and in blood. People with Alzheimer's disease, for example, have abnormally high levels of plaques made up of beta-amyloid and tangles made of tau proteins.

To look for earlier biomarkers of cognitive decline, a team led by Dr. Berislav V. Zlokovic at the University of Southern California, Los Angeles, examined two markers involved in the breakdown of the blood-brain barrier. This barrier controls the movement of cells and molecules between the blood and the fluid that surrounds the brain's nerve cells. Past studies have found that abnormalities in the small blood vessels (capillaries) of the brain often contribute to dementia.

The team enrolled more than 160 people with and without cognitive impairment. They measured levels of the soluble form of a protein called platelet-derived growth factor receptor beta (PDGFRβ). PDGFRβ is found in the capillaries that maintain the blood-brain barrier's integrity. Levels of the soluble form rise in cerebrospinal fluid when the blood-brain barrier is compromised. The team also tracked the integrity of the blood-brain barrier in 73 participants using an MRI-based technique they'd previously developed. The study was supported in part by NIH's National Institute on Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS). Results were published online on January 14, 2018, in Nature Medicine.

The researchers found that, compared with those without cognitive impairment, those with cognitive impairment had higher levels of soluble PDGFRβ and a greater breakdown in the blood-brain barrier of certain brain regions. Notably, both these measures were independent of beta-amyloid and tau protein levels. The findings suggest these measurements could pave the way for an early diagnostic test for cognitive impairment from Alzheimer's disease as well as other causes.

"This is a solid step towards an accurate and reliable test that could be an earliest sign of critical brain damage in some people with Alzheimer's disease and related dementias" says Dr. Roderick Corriveau, a program director at NINDS.

"Because of our aging population and growing public health concerns, efforts to find a reliable and accurate predictor of cognitive impairment and dementia are very important to researchers and the public," explains Dr. Suzana Petanceska, a program director at NIA. "These early results are showing one possible, promising way to quantify risk."

The researchers are planning to further validate these results by conducting a second trial with more participants.

This paper was funded in part by NIA grants R01AG023084, R01AG039452, P01AG052350, P50AG005142, RO1AG054434, R01AG055770, R21AG055034, P50AG05681, P01AG03991, and P01AG026276.

Reference: Nation DA, Sweeney MD, Montagne A, et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nature Medicine. 2019 Jan 14. doi: 10.1038/s41591-018-0297-y. [Epub ahead of print]