Research reveals cause of vascular changes associated with early Alzheimer’s

A Clemson University researcher and his international collaborators have discovered a cause of blood vessel damage in the brain that plays a role in Alzheimer's disease-related dementia.

Clemson Department of Physics and Astronomy Professor Feng Ding said the research, which was recently published in the journal Nature Communications, could lead to new therapeutic interventions.

The National Institutes of Health estimates that 6.7 million Americans aged 65 and older are living with Alzheimer's disease, a progressive, irreversible brain disorder and the most common type of dementia. It is the fifth leading cause of death for that age group.

A healthy brain contains tens of billions of neurons, which are specialized cells that process and transmit information via electrical and chemical signals. These cells send messages between the parts of the brain and from the brain to the muscles and organs of the body.

Communication disrupted

Alzheimer's disease disrupts this communication, resulting in widespread loss of brain function as many neurons stop working properly and eventually die. The cause of these changes may be tied to something called amyloid precursor protein, which is a protein that human bodies produce naturally.

When enzymes cut amyloid precursor protein into smaller molecules, amyloid beta monomers are one of the products. The problem comes when the amyloid beta monomers clump together to form toxic oligomers and eventually plaque near the neurons, resulting in loss of brain function.

Ninety-five percent of Alzheimer's disease patients also have plaque deposits in their cerebral blood vessels, which is called cerebral amyloid angiopathy.

Feng Ding, in the Clemson University College of Science Department of Physics and Astronomy, is conducting research on a protein linked to Alzheimer's disease. His research was published in the journal Nature.

Poking holes

The researchers found that oligomers can break into smaller nanoparticles that can harm the endothelium, or the blood-brain barrier.

"The endothelial cells connect with each other very tightly by the adherens and tight junctions and form this layer that constitutes the barrier separating the brain from blood circulation, known as the blood-brain barrier. We found that those oligomers can disrupt the adherens junctions between the endothelial cells and poke 'holes' in the otherwise 'seamless' layer, which allow the amyloid plaques to deposit on the surface of the blood vessel in the brain," Ding said. "This study shows why amyloid protein aggregation causes damage not just in the brain, but also in the vascular system. It provides an explanation for the extensive vascular damage observed in the aging brain."

Ding said the study reveals an additional target for better therapies for Alzheimer's disease.

Detailed findings from the research can be found in the paper "Endothelial leakiness elicited by amyloid protein aggregation" that appeared in the journal Nature Communications.

The work was financially supported by the National Institutes of Health (NIH) Awards R35GM145409 and P20GM121342. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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