Alzheimer's disease damages brain in two distinct phases: Study

Alzheimer's disease may progress in two distinct phases, with the early phase affecting specific brain cells before symptoms appear, and the later phase marked by rapid deterioration.

Alzheimer's disease may impact the brain in two distinct phases, according to a study by the US medical research agency, the National Institutes of Health.

Using advanced brain mapping tools, scientists have identified an early phase that occurs slowly and silently, affecting only a few types of brain cells before any noticeable memory problems arise.

In contrast, the later phase is more destructive, coinciding with the onset of symptoms and the rapid accumulation of plaques, tangles, and other markers of Alzheimer’s.

"One of the challenges to diagnosing and treating Alzheimer’s is that much of the damage happens well before symptoms occur. Now, for the first time, we can see what’s happening in the earliest stages of the disease,” said Dr Richard J. Hodes, Director of the NIH National Institute on Ageing.

This new understanding could help guide the development of more effective treatments.

The study, published in Nature Neuroscience, involved analysing the brains of 84 people. It suggests that damage to a specific type of brain cell called inhibitory neurons during the early phase may trigger the brain circuit disruptions that lead to Alzheimer’s.

The research confirmed previous findings about how the disease progresses while also uncovering new changes that occur in the brain during the disease's development.

Researchers used cutting-edge genetic analysis tools to study cells in the brain’s middle temporal gyrus, a region responsible for language, memory, and vision.

This part of the brain is known to be highly vulnerable to Alzheimer’s. By comparing data from healthy individuals to those with Alzheimer’s, the scientists were able to create a timeline of genetic and cellular changes throughout the disease.

One of the most surprising findings was the damage to somatostatin (SST) inhibitory neurons during the early phase.

Until now, scientists believed that Alzheimer’s primarily targeted excitatory neurons, which activate other brain cells. Inhibitory neurons, which calm other brain cells, appear to be more affected early on. The loss of these neurons may disrupt brain circuits and contribute to Alzheimer’s progression.

A separate NIH-funded study from MIT found that certain genes, such as REELIN, might make some neurons more vulnerable to Alzheimer’s.

The study also showed that astrocytes, star-shaped brain cells, could help resist the damage caused by the disease.

The research team, led by scientists from the Allen Institute in Seattle, studied over 3.4 million brain cells from donors at various stages of the disease.