Friday, January 25, 2019

By Staff Reports

 

LOS ANGELES (CNS)—Leaky capillaries in the brain portend early onset of Alzheimer's disease as they signal cognitive impairment before hallmark toxic proteins appear, according to a USC research study released Monday.

The findings, which appear in the current issue of Nature Medicine, could help with earlier diagnosis and suggest new targets for drugs that could slow down or prevent the onset of the disease, according to the researchers.

The number of Americans with Alzheimer's is expected to more than double to about 14 million in 40 years, according to the U.S. Centers for Disease Control and Prevention. There are currently five Alzheimer's drugs approved by the U.S. Food and Drug Administration that temporarily help with memory and thinking problems, but none that treat the underlying cause of the disease or slow its progression. Researchers believe that successful treatment will eventually involve a combination of drugs aimed at multiple targets.

USC's five-year study, which involved 161 older adults, showed that people with the worst memory problems also had the most leakage in their brain's blood vessels -- regardless of whether abnormal proteins amyloid and tau were present.

"The fact that we're seeing the blood vessels leaking, independent of tau and independent of amyloid, when people have cognitive impairment on a mild level, suggests it could be a totally separate process or a very early process," said senior author Berislav Zlokovic, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC. "That was surprising, that this blood-brain barrier breakdown is occurring independently."

In healthy brains, the cells that make up blood vessels fit together so tightly they form a barrier that keeps stray cells, pathogens, metals and other unhealthy substances from reaching brain tissue. Scientists call this the blood-brain barrier. In some aging brains, the seams between cells loosen, and the blood vessels become permeable.

"If the blood-brain barrier is not working properly, then there is the potential for damage," said co-author Arthur Toga, director of the USC Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine. "It suggests the vessels aren't properly providing the nutrients and blood flow that the neurons need. And you have the possibility of toxic proteins getting in."