• Posted October 17, 2024

Silent Damage First: Alzheimer's Disease Could Have Two Phases

Alzheimer’s disease might damage the brain in two distinct phases, a new study suggests.

An early phase that occurs slowly and silently appears to lay the groundwork for a second, more widely destructive phase of Alzheimer’s, according to sophisticated brain scans.

“The results fundamentally alter scientists’ understanding of how Alzheimer’s harms the brain and will guide the development of new treatments for this devastating disorder,” said Dr. Richard Hodes, director of the National Institute on Aging.

Previous studies have suggested that the damage caused by Alzheimer’s occurs in several stages, characterized by increasing levels of neuron death, inflammation and accumulation of toxic proteins in the brain.

But these results indicate there really are just two phases of Alzheimer’s, with most of the traditional symptoms and brain damage happening rapidly during the second phase, researchers said.

Brain scans of 84 people suggest that the first phase occurs prior to any memory problems that might develop.

During this phase, damage occurs to a type of brain cell called an inhibitory neuron that might trigger the neural problems that underlie Alzheimer’s, researchers said.

Inhibitory neurons send calming signals to other cells, researchers said. Losing these cells might strip the brain of a key level of protection.

The first phase also is marked by a slow accumulation of toxic protein plaques, activation of the brain’s immune system, and damage to the insulation that protects neurons.

“One of the challenges to diagnosing and treating Alzheimer’s is that much of the damage to the brain happens well before symptoms occur,” Hodes said. “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,”

Once the stage has been set, the second phase of Alzheimer’s ensues. People begin to develop overt memory and cognitive problems, and the damaging hallmarks of Alzheimer’s disease rapidly accumulate – amyloid beta plaques and tau tangles among them.

Researchers learned this by using advanced genetic analysis tools to study the cells of the middle temporal gyrus, a part of the brain that controls language, memory and vision. This region has been shown to be vulnerable to many of the changes caused by Alzheimer’s, and has been thoroughly mapped in previous research, researchers said.

By comparing healthy brains to those of Alzheimer’s patients, researchers created a genetic and cellular timeline of what happens throughout the disease.

The new study was published Oct. 14 in the journal Nature Neuroscience.

More information

The U.S. Centers for Disease Control and Prevention has more on Alzheimer’s disease.

SOURCE: National Institute on Aging, news release, Oct. 15, 2024