Alzheimer’s Progression May Occur in Two Phases, NIH Study Reveals

New research from the National Institutes of Health (NIH) indicates that Alzheimer’s disease may damage the brain in two distinct phases, reshaping scientists' understanding of how the disease progresses. Using advanced brain mapping tools funded by the NIH, researchers found that Alzheimer’s initially targets specific cell types early in its course, long before symptoms appear. This early phase progresses gradually and subtly, while a second phase—marked by widespread cell damage, plaques, and tangles—coincides with the onset of memory loss and other characteristic symptoms.

The study, published in Nature Neuroscience, analyzed over 3.4 million brain cells from 84 individuals at various stages of Alzheimer’s. Researchers focused on the middle temporal gyrus, a region associated with language, memory, and vision, and observed that inhibitory neurons, particularly somatostatin (SST) neurons, were among the earliest to show signs of damage. This finding challenges previous assumptions that excitatory neurons, which activate other cells, are the primary targets in Alzheimer’s. The loss of SST inhibitory neurons, which send calming signals, may disrupt neural circuits and contribute to disease progression.

By identifying these early cellular changes, scientists can now better understand how Alzheimer’s begins and develops before symptoms appear. This knowledge could support the creation of new research models and potentially lay the groundwork for therapies that focus on preserving neural function in Alzheimer’s patients.

This research showcases the potential of NIH’s BRAIN Initiative in advancing the understanding of neurodegenerative diseases. Dr. Richard Hodes, director of the NIH National Institute on Aging, noted that this study “fundamentally alters scientists’ understanding of how Alzheimer’s harms the brain,” which could guide future treatment approaches.