New research has revealed an early, hidden phase of Alzheimer’s disease, offering key insights into how the brain is damaged before memory loss and other symptoms appear.
This finding could change how scientists develop treatments and diagnose the disease.
Scientists from the Allen Institute for Brain Science in Seattle and the University of Washington Medicine conducted the study, examining brain tissue from 84 deceased Alzheimer’s patients.
Their findings, published in Nature Neuroscience, reveal that Alzheimer’s develops in two distinct phases.
The early phase, which occurs quietly, involves subtle cellular changes in the brain, while the more destructive second phase is when the disease’s classic symptoms, like memory loss, manifest.
Lead researcher Dr. Kyle Travaglini, Ph.D., explained, “Instead of looking at Alzheimer’s through the usual lens of plaques and tangles, we focused on how specific cell types were changed in each phase.” He and his team identified an early phase characterized by low levels of brain pathology without any signs of cognitive decline.
In this early phase, scientists found a gradual buildup of abnormal changes, including the loss of certain inhibitory neurons that were not previously linked to Alzheimer’s. These neurons act as brakes for brain activity and help maintain balance.
Dr. Travaglini described this as a “critical discovery” in understanding how the disease disrupts brain function.
The second phase of the disease, marked by extensive loss of neurons, is when patients typically begin to experience memory and cognitive issues. It is during this stage that the hallmark features of Alzheimer’s—plaques and tangles—build up rapidly, causing widespread brain damage.
Researchers also focused on the middle temporal gyrus (MTG), a brain region responsible for language, memory, and vision.
Using advanced machine learning technology, they compared brain samples from Alzheimer’s patients with those from healthy individuals. This allowed them to develop a “pathology clock” that maps out the disease’s progression over time.
Dr. Richard Hodes, director of the National Institute on Aging, highlighted the importance of understanding the early phase.
“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. Much of the brain damage occurs during this phase, long before symptoms are noticed, making it critical for early detection and intervention.
The study offers new hope for researchers and drug developers seeking to create treatments that could slow or prevent the progression of Alzheimer’s disease.
By identifying the earliest cellular changes, scientists aim to target therapies to specific stages of the disease, potentially delaying the onset of memory loss and cognitive decline.
Dr. Igor Camargo Fontana of the Alzheimer’s Association noted the broader implications of the findings. He highlighted that Alzheimer’s can begin causing damage 10 to 20 years before symptoms appear. If the early changes can be confirmed by further research, it raises the possibility of slowing or even preventing the progression to the second, more destructive phase of the disease.
The study, supported by the National Institute on Aging and the NIH BRAIN Initiative, marks a significant step forward in Alzheimer’s research and could change the way the disease is diagnosed and treated in the future.