ITHACA, N.Y. – Upon discovering the culprit of the decreased blood flow in the brain of people with Alzheimer's, the biomedical engineers at Cornell University have made possible promising new therapies for the disease.
Do you know that dizziness that you feel when, after going to bed for a prolonged period, you get up a little too fast?
That feeling is caused by a sudden reduction of blood flow to the brain, a reduction of about 30 percent. Now imagine that you live every minute of every day with that level of decreased blood flow.
People with Alzheimer's disease do not have to imagine it. The existence of reduced cerebral blood flow in patients with Alzheimer's disease has been known for decades, but the exact correlation with impaired cognitive function is less known.
"People probably adapt to the decreased blood flow, so they do not feel dizzy all the time, but there is clear evidence that it affects cognitive function," said Chris Schaffer, associate professor of biomedical engineering at Cornell University.
A new study from Schaffer's joint lab and associate professor Nozomi Nishimura offers an explanation for this dramatic decrease in blood flow: white blood cells stick to the inside of capillaries, the smallest blood vessels in the brain. And while only a small percentage of capillaries experience this blockage, each blocked vessel leads to a decrease in blood flow in multiple vessels downstream, which increases the impact on cerebral blood flow in general.
His article, "The adhesion of neutrophils in cerebral capillaries reduces cortical blood flow and affects memory function in mouse models with Alzheimer's disease", published in Nature neuroscience.
The co-authors of the article are Jean Cruz-Hernández, Ph.D., now a postdoctoral researcher at the Harvard Medical School, and Oliver Bracko, associate researcher at the Schaffer-Nishimura Laboratory.
The document, said Schaffer, is the culmination of approximately a decade of study, data collection and analysis. It started with a study in which Nishimura tried to put clots in Alzheimer's brain brain vasculature to see its effect.
"It turns out that … the blocks we were trying to induce were already there," he said. "In some way the research changed, this is a phenomenon that was already happening."
Recent studies suggest that deficits in cerebral blood flow are one of the first detectable symptoms of dementia.
"What we have done is to identify the cellular mechanism that causes the reduction of cerebral blood flow in models of Alzheimer's disease, which are neutrophils. [white blood cells] getting into the capillaries, "said Schaffer. We have shown that when we block the cellular mechanism [that causes the stalls], we get an improved blood flow, and associated with that improved blood flow is the immediate restoration of the cognitive performance of spatial and working memory tasks. "
"Now that we know the cellular mechanism," he said, "it's a much narrower path to identify the drug or the therapeutic approach to treat it."
The team has identified approximately 20 drugs, many of which are already approved by the FDA for human use, which have potential in the treatment of dementia and are now evaluating these drugs in mice with Alzheimer's.
Schaffer said he is "super optimistic" and that if the same mechanism of capillary blockage is at stake in humans than in mice, this line of research "could be a complete change for people with Alzheimer's disease."
This research was funded by the National Institutes of Health, the Alzheimer's Drug Discovery Foundation, the Alzheimer's Art Quilt Initiative, and the Brightfocus Foundation.
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