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It takes decades for a person's brain to be disabled by Alzheimer's disease. Now scientists have created a detailed timeline of what happens to different brain cells as the disease progresses. NPR's Jon Hamilton has this report.
JON HAMILTON, BYLINE: The Alzheimer's timeline is based on brain tissue from 84 people who died when they were 65 or older. Some had healthy brains, while others were in various stages of Alzheimer's. Ed Lein, of the Allen Institute for Brain Science, says a team of nearly 100 scientists studied more than 3.4 million brain cells.
ED LEIN: We measure all the genes in each individual cell. And that allows you to not only identify the cells but to look for changes in those cells as a function of disease.
HAMILTON: The team focused on cells in an area called the middle temporal gyrus, which is involved in language, memory and vision. Lein says one finding was that Alzheimer's progresses very slowly - at first.
LEIN: There are two clear phases. There's really an early phase where there's a very slow increase in the amount of pathology, it's very linear, and then a more exponential phase where suddenly things get really bad.
HAMILTON: Some of the early changes they saw merely confirmed earlier research. For example, cells related to immune function in the brain became more active. But Lein says artificial intelligence and new imaging techniques allowed the team to search for other changes that previously would have gone undetected.
LEIN: Essentially what we were looking for are vulnerable cell populations - for example, particular types of neurons that might be specifically lost early in disease.
HAMILTON: And Lein says they found one.
LEIN: It was quite a surprise, actually.
HAMILTON: Because it wasn't in the type of neuron the scientists were expecting. Lein says the team thought they might see changes in excitatory neurons, which act like the accelerator in a car by encouraging other neurons to fire.
LEIN: But it turns out that those are not the first cells lost. The first cells lost are actually some of the inhibitory neurons.
HAMILTON: Inhibitory neurons act like the brake in a car by limiting the activity of excitatory neurons. The team found that Alzheimer's affected a specific subset of inhibitory neurons that release a chemical messenger called somatostatin. These neurons help control the activity of brain networks involved in memory and thinking. Dr. Richard Hodes, who directs the National Institute on Aging, says the finding could be important because the brain needs to maintain a delicate balance between inhibitory and excitatory neurons.
RICHARD HODES: It could be that the loss of these inhibitory neurons is causing a hyperexcitatory state which may be contributing to disease.
HAMILTON: By unbalancing critical brain networks. Hodes says the study also suggests that the best time to treat Alzheimer's is very early on before these inhibitory neurons are lost.
HODES: The fact that there is a process early that is slow is an inviting opportunity to intervene.
HAMILTON: The research, which appears in the journal Nature Neuroscience, was funded largely by the National Institutes of Health BRAIN Initiative. Hodes says since President Obama launched the initiative in 2013, the Allen Institute and other research organizations have created tools and technology that allow increasingly detailed views of animal and human brains.
HODES: They've produced a picture of what's going on that no one could've anticipated just a few years ago.
HAMILTON: A picture that is now being used to understand human brain diseases, including Alzheimer's.
Jon Hamilton, NPR News.
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