Researchers closer to new Alzheimer's therapy with brain blood flow discovery

February 11, 2019

ITHACA, N.Y. - By discovering the culprit behind decreased blood flow in the brain of people with Alzheimer's, biomedical engineers at Cornell University have made possible promising new therapies for the disease.

You know that dizzy feeling you get when, after lying down for an extended period, you stand up a little too quickly?

That feeling is caused by a sudden reduction of blood flow to the brain, a reduction of around 30 percent. Now imagine living every minute of every day with that level of decreased blood flow.

People with Alzheimer's disease don't have to imagine it. The existence of cerebral blood flow reduction in Alzheimer's patients has been known for decades, but the exact correlation to impaired cognitive function is less understood.

"People probably adapt to the decreased blood flow, so that they don't feel dizzy all of the time, but there's clear evidence that it impacts cognitive function," said Chris Schaffer, associate professor of biomedical engineering at Cornell University.

A new study from the joint lab of Schaffer and associate professor Nozomi Nishimura, offers an explanation for this dramatic blood flow decrease: white blood cells stuck to the inside of capillaries, the smallest blood vessels in the brain. And while only a small percentage of capillaries experience this blockage, each stalled vessel leads to decreased blood flow in multiple downstream vessels, magnifying the impact on overall brain blood flow.

Their paper, "Neutrophil Adhesion in Brain Capillaries Reduces Cortical Blood Flow and Impairs Memory Function in Alzheimer's Disease Mouse Models," published in Nature Neuroscience.

The paper's co-lead authors are Jean Cruz-Hernandez, Ph.D., now a postdoctoral researcher at Harvard Medical School, and Oliver Bracko, a research associate in the Schaffer-Nishimura Lab.

The paper, Schaffer said, is the culmination of approximately a decade of study, data gathering and analysis. It began with a study in which Nishimura was attempting to put clots into the vasculatures of Alzheimer's mouse brains to see their effect.

"It turns out that ... the blockages we were trying to induce were already in there," she said. "It sort of turned the research around - this is a phenomenon that was already happening."

Recent studies suggest that brain blood flow deficits are one of the earliest detectable symptoms of dementia.

"What we've done is identify the cellular mechanism that causes reduced brain blood flow in Alzheimer's disease models, which is neutrophils [white blood cells] sticking in capillaries," Schaffer said. "We've 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 immediate restoration of 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 them already FDA approved for human use, that have potential in dementia therapy and are screening these drugs in Alzheimer's mice now.

Schaffer said he's "super-optimistic" that, if the same capillary-blocking mechanism is at play in humans as it is in mice, this line of research "could be a complete game-changer for people with Alzheimer's disease."
-end-
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.

Cornell University has dedicated television and audio studios available for media interviews supporting full HD, ISDN and web-based platforms.

Cornell University

Related Blood Flow Articles from Brightsurf:

Brain regions with impaired blood flow have higher tau levels
In Alzheimer's disease, impaired blood flow to brain regions coincides with tau protein buildup.

3D ultrasound enables accurate, noninvasive measurements of blood flow
A 3D ultrasound system provides an effective, noninvasive way to estimate blood flow that retains its accuracy across different equipment, operators and facilities, according to a new study.

Blood flow recovers faster than brain in micro strokes
Work by a Rice neurobiologist shows that increased blood flow to the brain is not an accurate indicator of neuronal recovery after a microscopic stroke.

Exercise improves memory, boosts blood flow to brain
Scientists have collected plenty of evidence linking exercise to brain health, with some research suggesting fitness may even improve memory.

3D VR blood flow to improve cardiovascular care
Biomedical engineers are developing a massive fluid dynamics simulator that can model blood flow through the full human arterial system at subcellular resolution.

MRI shows blood flow differs in men and women
Healthy men and women have different blood flow characteristics in their hearts, according to a new study.

Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia
A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.

Blood flow monitor could save lives
A tiny fibre-optic sensor has the potential to save lives in open heart surgery, and even during surgery on pre-term babies.

Changes in blood flow tell heart cells to regenerate
Altered blood flow resulting from heart injury switches on a communication cascade that reprograms heart cells and leads to heart regeneration in zebrafish.

Blood flow command center discovered in the brain
An international team of researchers has discovered a group of cells in the brain that may function as a 'master-controller' for the cardiovascular system, orchestrating the control of blood flow to different parts of the body.

Read More: Blood Flow News and Blood Flow Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.