Researchers Find New Alzheimer's Culprit and Potential Treatment Target

The discovery of the breakdown of the blood-brain barrier in Alzheimer's patients could lead to new, potential drug targets.

Alzheimer's is a devastating disease that wreaks havoc upon the brain and, unfortunately, it is not uncommon. According to the Alzheimer's Association, the disorder affected over 5.7 million people in the US alone in 2018.

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Even more worrisome is the fact that the Centers for Disease Control and Prevention expect the disease to reach about 14 million in the US in just 40 years. And so far the prognosis for effective treatment or a potential cure has been very poor.

Current Alzheimer’s drugs can do no more than help with memory and thinking problems. Up to now, no solution has been found to treat the underlying cause of Alzheimer's or even slow its devastating progression. 

That may soon be about to change thanks to University of Southern California (USC) researchers. The Alzheimer's team has stumbled on a potential new culprit for the neurodegenerative disorder that may also someday lead to a potential treatment target.

A blood-brain barrier breakdown

The team undertook a five-year study involving 161 older adults and discovered that the patients with the most severe memory problems also had the most leakage in their brain’s blood vessels. 

“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 adults, the blood-brain barrier sees the brain's blood vessels located so tightly they keep all dangerous substances from ever reaching brain tissue.

Toxic proteins getting in

“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 Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine.

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“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.”

Now the researchers are hoping that this new find could help with crucial earlier diagnosis and provide new potential treatment targets.  

“The results were really kind of eye-opening,” said first author Daniel Nation, an assistant professor of psychology at the USC Dornsife College of Letters, Arts and Sciences.

“It didn’t matter whether people had amyloid or tau pathology; they still had cognitive impairment.”

Now the team is focused on understanding how cognitive problems occur after this worrisome blood vessel damage occurs. The study is published in the journal Nature Medicine

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