Researchers Zero In on First, Subtle Phase of Alzheimer's

Alzheimer's disease appears to damage the brain in two phases, and treatment before the latter stage, when "suddenly things get really bad," is key. That's according to Ed Lein, a senior investigator at the Allen Institute for Brain Science, who worked with nearly 100 colleagues to analyze more than 3.4 million cells from the brains of 84 people who died age 65 or older, all but nine of whom had Alzheimer's disease, per Medical News Today. They identified an early phase of disease "where there's a very slow increase in the amount of pathology," Lein tells NPR, adding he was surprised to see that the first cells to die off are a small subset of neurons known as somatostatin inhibitory neurons, which have largely been overlooked.

That early stage of disease—also marked by the slow accumulation of plaques and activation of cells related to immune function but no cognitive effects—is followed by a second stage with "many of the traditionally studied changes [related to Alzheimer's] happening rapidly," coinciding "with the appearance of memory problems and other symptoms," according to a release from National Institute on Aging, which helped fund the research. Therefore, Lein and colleagues suggest treatments are most likely to be beneficial when started before the second stage. They also suggest protecting vulnerable inhibitory neurons might make a difference, according to the study published last month in Nature Neuroscience.

While excitatory neurons activate other neurons when sending electrical signals through the brain, inhibitory neurons restrain other neurons, making them less likely to fire. The two essentially balance each other out, but disruptions in this so-called global excitatory/inhibitory balance are thought to trigger brain disorders. "It could be that the loss of these [somatostatin] inhibitory neurons is causing a hyper-excitatory state which may be contributing to disease," NIA Director Dr. Richard Hodes tells NPR. These particular inhibitory neurons release a chemical called somatostatin, "which is known to decline in Alzheimer's patients," per the outlet. They're also largely confined to the brain region associated with memory, vision, and language, per MNT. (More Alzheimer's disease stories.)