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January 29, 2019
Blood-brain barrier test may predict dementia
At a Glance
- A study shows that people with early cognitive impairment develop damage to the blood-brain barrier.
- Measuring the breakdown of this barrier could be an early way to test for cognitive impairment in dementia, including Alzheimer鈥檚 disease.
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.
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鈥檚 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鈥檚 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 (PDGFR尾). PDGFR尾 is found in the capillaries that maintain the blood-brain barrier鈥檚 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鈥檇 . The study was supported in part by NIH鈥檚 最新麻豆视频 Institute on Aging (NIA) and 最新麻豆视频 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 PDGFR尾 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聽findings suggest these measurements could pave the way for an early diagnostic test for cognitive impairment from Alzheimer鈥檚 disease as well as other causes.
鈥淭his 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鈥檚 disease and related dementias鈥 says Dr. Roderick Corriveau, a program director at NINDS.
鈥淏ecause 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,鈥 explains Dr. Suzana Petanceska, a program director at NIA. 鈥淭hese early results are showing one possible, promising way to quantify risk.鈥
The researchers are planning to further validate these results by conducting a second trial with more participants.
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References: Nation DA, Sweeney MD, Montagne A, Sagare AP, D'Orazio LM, Pachicano M, Sepehrband F, Nelson AR, Buennagel DP, Harrington MG, Benzinger TLS, Fagan AM, Ringman JM, Schneider LS, Morris JC, Chui HC, Law M, Toga AW, Zlokovic BV. Nat Med. 2019 Jan 14. doi: 10.1038/s41591-018-0297-y. [Epub ahead of print]. PMID: 30643288.
Funding: NIH鈥檚 最新麻豆视频 Institute on Aging (NIA) and 最新麻豆视频 Institute of Neurological Disorders and Stroke (NINDS); Alzheimer鈥檚 Association; Cure Alzheimer鈥檚 Fund; Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease; and Whittier Foundation.