Healthy blood vessels are the key to brain health in old age


If you’re worried about Alzheimer’s disease, your best shot at prevention could be maintaining cardiovascular health through exercise and diet and staying on top of conditions such as diabetes and high blood pressure.

That’s because USC researchers suspect healthy blood vessels are the key to brain health in old age.

Their work shows that damaged capillaries in the brain – rather than plaques and tangles of abnormal proteins – may set the stage for Alzheimer’s decades before memory problems emerge.

This work – as well as the latest findings from dozens of other USC Alzheimer’s scientists -will be on display at the Alzheimer’s Association International Conference, which will be held July 14-18 at the Los Angeles Convention Center.

Alzheimer’s is considered one of the greatest health challenges of the century, affecting an estimated 5.4 million Americans.

“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 Berislav Zlokovic, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC.

How understanding the blood-brain barrier can help with Alzheimer’s prevention

In healthy brains, the cells that form the walls of capillaries fit tightly together to form a barrier that keeps stray cells, pathogens, metals and other unhealthy substances from reaching brain tissue.

Scientists call this the blood-brain barrier.

In some aging brains, the seams between cells loosen, blood vessels become permeable and neurons begin to die.

“We’ve also learned that pericytes, a type of cell in the blood-brain barrier, not only help push blood through the brain but also secrete a substance that protects neurons,” Zlokovic said.

Zlokovic works closely with Arthur Toga, a world leader in mapping brain structure and functioning, who directs the USC Mary and Mark Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine.

“Brain imaging is integral to studying Alzheimer’s disease.

In visualizing the blood-brain barrier in people, we actually can see and measure changes where the barrier breaks down,” Toga said.

“We’ve been able to correlate greater leakage with increased cognitive decline.”

In addition, brain imaging is allowing Toga to detect changes, potentially indicative of disease, in the spaces around blood vessels in the brain. Known as perivascular spaces, they help drain fluid and metabolic waste from the brain.

Exploring additional USC research into healthy brains

Other USC scientists are also working at the intersection of blood vessels and brain health, including Diana Younan, a senior research associate in the department of preventive medicine at the Keck School of Medicine.

She studies the link between air pollution and dementia.

The exact mechanism isn’t fully understood; for instance, does fine particle pollution penetrate the blood-brain barrier and infiltrate brain tissue?

Is it a matter of pollution triggering inflammation?

In her recent research, Younan looked at this association and explored the protective effects of higher levels of education, physical activity and challenging work – all of which contribute to “cognitive reserve,” or resilience in the brain’s function.

When she and her colleagues studied people exposed to fine particle pollution, they found that higher levels of cognitive reserve seemed to protect against dementia.

“Here in Los Angeles, you can’t really avoid air pollution,” Younan said.

“So, if people are staying involved in mentally stimulating activities, it could decrease the risk of memory problems later on.”

Daniel Nation, an assistant professor of psychology at the USC Dornsife College of Letters, Arts and Sciences, found that patients with untreated diabetes developed signs of Alzheimer’s disease 1.6 times faster than people who did not have diabetes.

One theory is that diabetes treatment may keep the brain’s blood vessels healthy, staving off dementia.

“It’s clear that the medicines for treating diabetes make a difference in the progression of dementia,” Nation said. “

But it’s unclear how exactly those medications slow or prevent the onset of Alzheimer’s disease, so that is something we need to investigate.”

Key Biological Processes in the Brain

Most neurons have three basic parts: a cell body, multiple dendrites, and an axon.

  • The cell body contains the nucleus, which houses the genetic blueprint that directs and regulates the cell’s activities.
  • Dendrites are branch-like structures that extend from the cell body and collect information from other neurons.
  • The axon is a cable-like structure at the end of the cell body opposite the dendrites and transmits messages to other neurons.

The function and survival of neurons depend on several key biological processes:

  • Communication. Neurons are constantly in touch with neighboring brain cells. When a neuron receives signals from other neurons, it generates an electrical charge that travels down the length of its axon and releases neurotransmitter chemicals across a tiny gap, called a synapse. Like a key fitting into a lock, each neurotransmitter molecule then binds to specific receptor sites on a dendrite of a nearby neuron. This process triggers chemical or electrical signals that either stimulate or inhibit activity in the neuron receiving the signal. Communication often occurs across networks of brain cells. In fact, scientists estimate that in the brain’s communications network, one neuron may have as many as 7,000 synaptic connections with other neurons.
  • Metabolism. Metabolism—the breaking down of chemicals and nutrients within a cell—is critical to healthy cell function and survival. To perform this function, cells require energy in the form of oxygen and glucose, which are supplied by blood circulating through the brain. The brain has one of the richest blood supplies of any organ and consumes up to 20 percent of the energy used by the human body—more than any other organ.
  • Repair, remodeling, and regeneration. Unlike many cells in the body, which are relatively short-lived, neurons have evolved to live a long time—more than 100 years in humans. As a result, neurons must constantly maintain and repair themselves. Neurons also continuously adjust, or “remodel,” their synaptic connections depending on how much stimulation they receive from other neurons. For example, they may strengthen or weaken synaptic connections, or even break down connections with one group of neurons and build new connections with a different group. Adult brains may even generate new neurons—a process called neurogenesis. Remodeling of synaptic connections and neurogenesis are important for learning, memory, and possibly brain repair.

Neurons are a major player in the central nervous system, but other cell types are also key to healthy brain function.

In fact, glial cells are by far the most numerous cells in the brain, outnumbering neurons by about 10 to 1.

These cells, which come in various forms – such as microglia, astrocytes, and oligodendrocytes – surround and support the function and healthy of neurons.

For example, microglia protect neurons from physical and chemical damage and are responsible for clearing foreign substances and cellular debris from the brain.

To carry out these functions, glial cells often collaborate with blood vessels in the brain.

Together, glial and blood vessel cells regulate the delicate balance within the brain to ensure that it functions at its best.

Vascular Contributions to Alzheimer’s Disease

People with dementia seldom have only Alzheimer’s-related changes in their brains.

Any number of vascular issues – problems that affect blood vessels, such as beta-amyloid deposits in brain arteries, atherosclerosis (hardening of the arteries), and mini-strokes – may also be at play.

Vascular problems may lead to reduced blood flow and oxygen to the brain, as well as a breakdown of the blood-brain barrier, which usually protects the brain from harmful agents while allowing in glucose and other necessary factors.

In a person with Alzheimer’s, a faulty blood-brain barrier prevents glucose from reaching the brain and prevents the clearing away of toxic beta-amyloid and tau proteins.

This results in inflammation, which adds to vascular problems in the brain.

Because it appears that Alzheimer’s is both a cause and consequence of vascular problems in the brain, researchers are seeking interventions to disrupt this complicated and destructive cycle.

Provided by University of Southern California


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