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By discovering the cause of decreased blood flow in the brains of people with Alzheimer's disease, Cornell's biomedical engineers have made possible new therapies promising for the disease.
Do you know that your head is spinning when, after lying down for a long time, you get up a little too fast?
This sensation is caused by a sudden reduction in blood flow to the brain, a reduction of about 30%. Now, imagine living every minute of every day with this level of decreased blood flow.
People with Alzheimer's disease do not have to imagine it. The existence of a reduction in cerebral blood flow in patients with Alzheimer's disease has been known for decades, but the exact correlation with impaired cognitive function is less well understood.
"People probably adapt to decreased blood flow, so that they do not feel stunned all the time, but it is clearly established that this has an impact on cognitive function," he said. Chris Schaffer, Associate Professor of Biomedical Engineering at Cornell University.
A new study from Schaffer's joint lab and badociate professor Nozomi Nishimura provides an explanation for this dramatic decrease in blood flow: white blood cells stuck inside the capillaries, the smallest blood vessels in the brain. And while only a small percentage of capillaries undergo this blockage, each blocked vessel causes a decrease in blood flow in several downstream vessels, amplifying the impact on overall cerebral blood flow.
Their article, "Adherence of neutrophils in cerebral capillaries, reduces cortical blood flow and alters memory function in murine models with Alzheimer's disease", published in Nature Neuroscience.
The lead co-authors of the document are Dr. Jean Cruz-Hernandez, now a postdoctoral fellow at Harvard Medical School, and Oliver Bracko, research badociate at Schaffer-Nishimura Laboratory.
The document, said Schaffer, is the culmination of about a decade of studies, data collection and badysis. It started with a study in which Nishimura was trying to put clots in the blood vessels of the Alzheimer's mouse brain to see their effect.
"It turned out that (…) the blockages we were trying to induce were already there," she said. "This has somehow reversed the search – it's a phenomenon that was already happening."
Recent studies suggest that cerebral blood flow deficits are one of the first detectable symptoms of dementia.
"What we did is identify the cellular mechanism that causes reduced cerebral blood flow in models of Alzheimer's disease, namely neutrophils. [white blood cells] sticky in the capillaries, "said Schaffer." We showed that when we block the cellular mechanism [that causes the stalls], we obtain an improvement of the blood circulation, and badociated with this improvement of the blood flow, an immediate restoration of the cognitive performances of the tasks of spatial memory and work. "
"Now that we know the cellular mechanism," he said, "it's a much narrower way to identify the drug or the therapeutic approach to treat it."
The team has identified approximately 20 drugs, many of which have already been approved by the FDA for human use, that could be useful in the treatment of dementia and are currently being tested in the Alzheimer's mice.
Schaffer said it is "super optimistic" that, if the same mechanism of hair blockage is at play in humans as in the mouse, this line of research "could completely change the situation 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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