U��֦��Ƶ researchers find important clues contributing to Alzheimer's disease

April 1, 2025

U��֦��Ƶ researchers find important clues contributing to Alzheimer's disease

How the brain interacts with the vascular system may be key to reducing disease risk

Minh Dang Nguyen (left) and Milène Vandal standing in front of the Hotchkiss Brain Institute sign in the Cumming School of Medicine.

Principal investigator Minh Dang Nguyen, left, and Milène Vandal, first author on Neuron paper that finds vascular system holds clues to Alzheimer's. Quentin Collier, Department of Clinical Neurosciences

According to the Alzheimer's Society of Canada, one in four Canadians over the age of 85 is living with dementia — and Alzheimer’s disease (AD) accounts for more than 60 per cent of those cases.

Though Alzheimer’s disease is often described as a buildup of proteins in the brain in the form of plaques and tangles, a new study by ��֦��Ƶ researchers has shown that blood vessels in the brain might hold another important clue to the disease.

The discovery, which focused on a protein called CD2AP, could dramatically change how the disease is perceived and treated, says the study’s principal investigator, Dr. , PhD, a professor in the and a member of the at the

The image shows a healthy brain cell in multiple colors, there is a large presentation of the color red, which indicates the presence of CD2AP protiens.

Image of a healthy brain vessel with high levels of CD2AP protein shown in red

Louise Reveret, co-author on study

Nguyen compares the brain’s vascular system to a tree. The complex branches—arteries, capillaries and veins—are critical to delivering nutrients throughout the brain. The cerebrovascular system in AD patients, he says, doesn’t deliver those nutrients properly.

AD may be more related to diseases of the vascular system, such as arteriosclerosis or diabetes, than anticipated, he says.

Nguyen says the discovery, published in the journal , reveals important factors to consider about how the brain interacts with the vascular system and, particularly, the cells that form the brain blood vessels, called brain endothelial cells.

Importantly, the researchers discovered that the levels of CD2AP are reduced in brain blood vessels of patients who died with AD.

“The lower the levels, the worse was their memory function prior to death,” says Nguyen. “This correlation is particularly striking in males.”

The researchers dived deeper and applied what they observed in human samples to studies using mice that have altered levels of CD2AP.

“We saw a lot of differences in how the vasculature was functioning related to CD2AP levels with consequences on memory function,” says Dr. Milène Vandal, PhD, first author on the study.

In fact, says Vandal, CD2AP may be protective for females, adding to the sex-dependent result. More research into new approaches based on sex may be needed.

“If you're trying to improve the vascular system of a person to reduce their risk of AD, you might want to have different strategies for men and women, because their vascular system is just not reacting the same way,” she says.

While this discovery could lead to future treatments that target CD2AP—at least in half the population—Vandal says the timeline for most new drugs is very long.

Instead, the researchers say there are easier ways to reduce the risk of AD and all other vascular diseases.

“I think the immediate strategy is, really, take care of yourself and your lifestyle—anything that affect the vascular system,” says Nguyen. “A good diet, exercise, less stress and better sleep—interventions that work for both sexes.”

The , led by U��֦��Ƶ, involved a collaboration of researchers from Canada, the United States, Germany and Korea.

Minh Dang Nguyen is a professor in the departments of Clinical Neurosciences, Cell Biology & Anatomy, and Biochemistry & Molecular Biology at the Cumming School of Medicine (CSM). He is a member of the Alberta Children's Research Institute and Hotchkiss Brain Institute at the CSM.