New research suggests that Alzheimer’s disease damages the brain in two separate phases, with the first phase happening slowly and quietly before any symptoms appear, while the second phase leads to rapid and widespread damage.
This discovery, made possible by advanced brain-mapping techniques, could change how scientists understand and treat Alzheimer’s.
For years, researchers have believed that Alzheimer’s causes brain damage in a series of gradual stages, marked by progressive cell death, inflammation, and the buildup of plaques and tangles. However, this study, published in Nature Neuroscience, suggests that the disease actually unfolds in two distinct phases.
In the early phase, damage happens at a slow rate, affecting only a few types of brain cells. Inhibitory neurons, which help regulate brain activity, appear to be among the first cells affected.
At this stage, plaques begin forming, the brain’s immune system becomes activated, and the insulation around nerve cells starts to break down, but the changes are subtle and do not yet cause noticeable memory problems.
The second phase is when the disease becomes more aggressive. This stage coincides with the appearance of memory loss and other symptoms. At this point, damage spreads quickly across the brain, more neurons die, and the plaques and tangles accumulate rapidly.
Scientists believe that losing inhibitory neurons in the first phase may disrupt brain activity, triggering the cascade of problems seen in the second phase.
To better understand how Alzheimer’s progresses, researchers studied brain tissue from 84 people, comparing those with the disease to healthy individuals. They focused on a brain region called the middle temporal gyrus, which is important for language, memory, and vision and is known to be especially vulnerable in Alzheimer’s.
Using genetic analysis tools, they mapped more than 3.4 million brain cells, creating a detailed timeline of how the disease affects different cell types over time. The findings confirmed what scientists already knew about how Alzheimer’s damages the brain but also revealed new insights.
One surprising discovery was that inhibitory neurons—specifically a type called somatostatin (SST) inhibitory neurons—are among the first to die in Alzheimer’s. Traditionally, researchers believed that excitatory neurons, which send activating signals, were the primary target of the disease.
However, this study suggests that losing inhibitory neurons early on may be a key trigger for the brain dysfunction that follows.
The study also builds on recent findings from MIT, where researchers identified a gene called REELIN that may make some neurons more vulnerable to Alzheimer’s. Their work also suggested that astrocytes, star-shaped support cells in the brain, might help protect against the disease.
This research is part of a larger project called the Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD), which aims to create a highly detailed map of how Alzheimer’s affects different parts of the brain.
Scientists used tools developed through the NIH’s Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which has provided new ways to study diseases at the cellular level.
According to Dr. Richard Hodes, director of the National Institute on Aging, this study is a game-changer for Alzheimer’s research. Being able to detect early brain changes before symptoms appear opens new possibilities for early diagnosis and treatment.
This could lead to new therapies aimed at slowing or stopping the disease before irreversible damage occurs.
The research team believes these findings will help scientists and drug developers create treatments specifically targeted to different phases of Alzheimer’s. Right now, most Alzheimer’s treatments focus on managing symptoms after significant damage has already occurred.
But if doctors can detect and address the first phase of the disease early, it may be possible to prevent the second, more destructive phase from happening.
This study represents a major step forward in understanding Alzheimer’s. While there is still much to learn, the discovery of these two distinct phases gives researchers a new roadmap for developing better diagnostics and treatments, offering hope for slowing or preventing the devastating effects of the disease.
If you care about Alzheimer’s disease, please read studies about the protective power of dietary antioxidants against Alzheimer’s, and eating habits linked to higher Alzheimer’s risk.
For more information about brain health, please see recent studies that oral cannabis extract may help reduce Alzheimer’s symptoms, and Vitamin E may help prevent Parkinson’s disease.
The research findings can be found in Nature Neuroscience.
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