Leaky capillaries in the brain may be an early sign of Alzheimer’s disease, according to a new study published in the journal Nature Medicine.
These leaky blood vessels, which represent a breakdown of the blood-brain barrier, were consistently linked to cognitive impairment in study participants, regardless of whether the hallmark toxic proteins amyloid and tau were present.
The findings could help with earlier diagnosis and suggest new targets for drugs that could slow down or even prevent disease onset.
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. This is known as 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 University of Southern California (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.”
The five year-study showed that older adults 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 Dr. Berislav Zlokovic, director of USC’s Zilkha Neurogenetic Institute at the Keck School of Medicine.
“That was surprising that this blood-brain barrier breakdown is occurring independently.”
For the study, 161 older adults had their memory and thinking abilities evaluated through a series of tasks and tests, resulting in measures of cognitive function and a “clinical dementia rating score.”
Those diagnosed with disorders that might account for cognitive impairment were excluded from the study. The researchers used neuroimaging and cerebral spinal fluid analysis to measure the permeability, or leakiness, of capillaries serving the brain’s hippocampus, and discovered a strong link between impairment and leakage.
“The results were really kind of eye-opening,” said first author Dr. 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.”
The researchers warn that the results represent a snapshot in time. Moving forward, they hope to get a better sense of how early cognitive problems occur after blood vessel damage appears.
Zlokovic said it’s unlikely that scientists will soon abandon amyloid and tau as Alzheimer’s biomarkers, “but we should be adding some vascular biomarkers to our toolkit.”
Currently, there are 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.