Scientists map brain changes to better treat Alzheimer’s disease: pictures

The scientists say Alzheimer’s research needs to take a broader look at how the disease affects the brain — whether it’s changes in the cortex or the role of inflammation.

Matt York/AP

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Matt York/AP

The scientists say Alzheimer’s research needs to take a broader look at how the disease affects the brain — whether it’s changes in the cortex or the role of inflammation.

Matt York/AP

The field of Alzheimer’s research is branching out.

After decades of focusing on the sticky amyloid plaques and tangled tau fibers associated with the disease, brain researchers are looking for other potential causes of impaired memory and thinking.

That search is on full display this week at the Alzheimer’s Association International Conference in San Diego, where sessions examine factors including genes, brain damage, clogged arteries and inflammation.

A group of researchers in Seattle even unveiled a very detailed atlas showing how different types of brain cells change in Alzheimer’s. The goal is to help scientists identify new treatment approaches.

“Of course, plaques and tangles are a hallmark,” says Maria Carrillo, chief scientific officer of the Alzheimer’s Association. “This does not mean that the plaques are the cause of the cell death.”

Plaques are clumps of a protein called beta-amyloid that appear in the spaces between neurons. The tangles are made up of a protein called tau that occurs inside a neuron.

Both proteins tend to accumulate in the brains of people with Alzheimer’s. But their role in killing brain cells is still unclear.

Carrillo says the Alzheimer’s field needs to turn to cancer research, where a deeper understanding of the disease has led to better treatments.

The change comes after a series of experimental drugs succeeded in removing amyloid plaques and tau tangles from the brain but failed to stop the disease.

The Food and Drug Administration has approved one drug for amyloid, Aduhelm, but is still evaluating whether it really helps patients.

Alzheimer’s Atlas

The study that created the atlas is emblematic of how researchers are recalibrating.

“What we’re trying to do with this study is look at cellular vulnerability early in the disease, before [people] they have plaques and tangles before they have cognitive impairment,” says Dr. C. Dirk Keene, a neuropathologist at the University of Washington.

To create the atlas, Keane and a team of researchers analyzed more than a million cells from 84 brains donated by people who had enrolled in Alzheimer’s research projects led by the University of Washington and the Kaiser Permanente Washington Research Institute.

The brains come from donors “at all different stages of the disease,” Keane says, “so we can determine what’s going on from the earliest levels to people with advanced disease.”

The effort is funded by the National Institute on Aging and is an outgrowth of the federal BRAIN initiative launched by President Obama in 2013.

The atlas came from the realization that “If we want to treat diseases of an extremely complex cellular organ, you have to understand that organ much better than we do,” says Ed Lane, a senior researcher at the Allen Institute for Brain Sciences who plays a key role in brain tissue analysis.

So the team spent years studying cells in healthy brains before looking at brains affected by Alzheimer’s.

“We’ve determined what a normal adult brain looks like,” says Lane, “and now we can use that knowledge and look for changes that happen in specific types of cells.”

Detection of vulnerable brain cells

At the Alzheimer’s meeting, the team described the changes they saw in more than 100 types of cells taken from the cerebral cortex, an area of ​​the brain that is important for memory and thinking.

One finding is that neurons that make connections within the cortex itself are much more likely to die than those that connect to distant areas of the brain.

“What we’re seeing is a profound effect on cortical circuits that very plausibly is why we have cognitive decline,” says Lane.

If so, a treatment designed to protect these vulnerable neurons could prevent the declines in memory and thinking associated with Alzheimer’s disease.

The team also found a proliferation of brain cells that contribute to inflammation. These include certain immune cells and a type of cell that responds to injury.

“So while the neurons are being lost, the non-neuronal cells are actually increasing and changing,” says Lane.

The finding supports the idea that inflammation plays an important role in Alzheimer’s disease and that anti-inflammatory drugs can help protect the brain.

The Seattle team hopes other scientists will use the brain cell atlas to suggest new treatments for Alzheimer’s.

“We’ve created an open access resource where the whole community can come and look at this data,” says Lane. “They can mine it to accelerate progress in the field as a whole.”

Accelerating progress is one reason Kyle Travalini, a researcher at the Allen Institute, jumped at the chance to work on the Alzheimer’s project.

“My grandmother started developing Alzheimer’s when I was just going to college,” says Travalini, who received his Ph.D. in 2021.

Travallini says the atlas project is appealing because it’s not based on a preconceived idea of ​​what causes Alzheimer’s.

“It’s like looking at the same disease that everyone has looked at, but in a completely different way,” he says.

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