Story By Jaye Kenzie–SHWRT

Recent findings have shed light on the impact of Alzheimer’s disease on the brain.

A team led by the Allen Institute for Brain Science and the University of Washington Medicine has pinpointed cellular alterations in the brains of individuals with the disease, along with a timeline of these changes.

“Rather than examining Alzheimer’s Disease solely in terms of plaques and tangles, we concentrated on the alterations in specific cell types during each stage of the disease,” declared Dr. Kyle Travaglini, Ph.D., a researcher at the Allen Institute.

“ALZHEIMER’S DISEASE COULD BE SLOWED BY BOOSTING A CERTAIN PROTEIN IN THE BRAIN, RESEARCHERS SAY“

“Two primary phases in Alzheimer’s Disease have been identified by arranging donors on a continuous disease trajectory: an initial slow phase characterized by minimal pathology and no cognitive decline, and a subsequent phase marked by a significant increase in pathology and cognitive deterioration.”

The research, recently published in Nature Neuroscience, analyzed millions of cells from the brain tissue donated by 84 individuals who had passed away with Alzheimer’s disease. The cases varied from mild, asymptomatic stages to advanced dementia.

“Through the study of research subjects at various stages of Alzheimer’s disease, including the earliest phases, our aim is to pinpoint the vulnerable cells at the onset of the disease, well before any symptoms manifest,” stated C. Dirk Keene, a neuropathology professor at UW Medicine, in a press release.

Researchers focused on the middle temporal gyrus (MTG) — the part of the brain that controls language, memory, and vision.

That portion of the brain is known as a “critical transition zone,” where evidence of Alzheimer’s appears and then worsens as the disease progresses.

Using machine learning technology, researchers compared the cells, genes and DNA of the Alzheimer’s brain samples to maps of the normal brain generated by the Allen Institute.

“Utilizing these tools, scientists have detected the initial cellular alterations in the brain, providing a more comprehensive understanding of the disease’s progression,” stated John Ngai, Ph.D., director of The BRAIN Initiative, in the announcement.

“The new knowledge provided by this study may help scientists and drug developers around the world develop diagnostics and treatments targeted to specific stages of Alzheimer’s and other dementias,” he added.

The study identified “two distinct phases” of Alzheimer’s disease.

“You could say we created a pathology clock that tells not only what changes are happening in this cortical region, but when,” said Mariano Gabitto, Ph.D., a lead author and assistant investigator at the Allen Institute, in the release.

First, there was a “slow, early buildup of abnormal cellular changes,” the researchers noted.

During this period, the patient may not experience any symptoms of memory loss or cognitive decline.

In that first phase, the researchers were surprised to discover the loss of certain inhibitory neurons that were not previously linked to Alzheimer’s.

Travaglini described that as a “critical discovery,” as those neurons act as “brakes” for brain activity and “keep things balanced.”

“This specificity gives us new clues about how and why certain brain circuits could break down in AD,” he said.

Richard J. Hodes, MD, director of the NIH National Institute on Aging, noted that one of the challenges in diagnosing and treating Alzheimer’s is that much of the damage to the brain happens in this early phase, before symptoms occur.

“The ability to detect these early changes means that, for the first time, we can see what is happening to a person’s brain during the earliest periods of the disease,” he said in the release.

The second phase was marked by a “much more extensive loss” of different types of neurons and cells, leading to the accumulation of the hallmark “plaques and tangles” in the brain — which is typically when patients begin to notice cognitive decline.

Igor Camargo Fontana, Ph.D., Alzheimer’s Association director of scientific conference programming in Chicago, was not involved in the study but shared what he described as the “bigger picture” it revealed.

“Alzheimer’s disease is characterized by a lengthy pre-symptomatic phase; changes associated with Alzheimer’s occur in the brain 10, 15, or even 20 years before the emergence of memory and cognitive symptoms,” he explained.

“If the findings in this new paper are confirmed by other labs, it raises the question of whether effectively addressing the brain changes that happen in what the authors call the first ‘quiet’ phase can slow, delay, or prevent the second, more destructive phase.”

Looking ahead, Fontana says it will be important to further investigate the “quiet” phase to confirm how it’s linked to the better-known biomarkers of Alzheimer’s, such as amyloid and tau.