Attention, nerve cells: It’s not all about you.
As a new study in the Journal of Clinical Investigation led by Stanford neuroscientist Kati Andreasson, MD, shows, blocking the action of a single molecule situated on the surfaces of entirely different brain cells reversed memory loss and a bunch of other Alzheimer’s-like features in experimental mice.
The very term “neuroscience” strongly suggests that nerve cells, a.k.a. neurons, are the Big Enchilada in brain research – and, let’s face it, you wouldn’t want to leave home without them. But they’re far from the entire picture. In fact, neurons account for a mere 10 percent of all the cells in the brain. It may be that the mass die-off of nerve cells in the brains of people with Alzheimer’s disease may largely occur because, during the course of aging, another set of key players ensconced in that mysterious organ inside our skull and known collectively as microglia begin to fall down on the job.
In a release I wrote to explain the study’s findings in lay terms, I described microglia as the brain’s very own, dedicated immune cells:
A microglial cell serves as a front-line sentry, monitoring its surroundings for suspicious activities and materials by probing its local environment. If it spots trouble, it releases substances that recruit other microglia to the scene … Microglia are tough cops, protecting the brain against invading bacteria and viruses by gobbling them up. They are adept at calming things down, too, clamping down on inflammation if it gets out of hand. They also work as garbage collectors, chewing up dead cells and molecular debris strewn among living cells – including clusters of a protein called A-beta, notorious for aggregating into gummy deposits called Alzheimer’s plaques, the disease’s hallmark anatomical feature. … A-beta, produced throughout the body, is as natural as it is ubiquitous. But when it clumps into soluble clusters consisting of a few molecules, it’s highly toxic to nerve cells. These clusters are believed to play a substantial role in causing Alzheimer’s.
“The microglia are supposed to be, from the get-go, constantly clearing A-beta, as well as keeping a lid on inflammation,” Andreasson told me. If their job performance heads downhill – as seems to occur during the aging process – things get out of control. A-beta builds up in the brain, inducing toxic inflammation.
But by blocking the activity of a single molecule – a receptor protein on microglial cells’ surfaces – Andreasson’s team got those microglia back on the job. They resumed chewing up A-beta, quashing runaway neuro-inflammation, squirting out neuron-nurturing chemicals. Bottom line: the Alzheimer’s-prone experimental animals’ IQs (as measured by mousey memory tests) rose dramatically.
Aspirin and similar drugs also tend to shut down the activity of this microglial receptor, which may or may not explain why their use seems to stave off the onset of Alzheimer’s in people who start using them regularly (typically for unrelated reasons) before this memory-stealing syndrome’s symptoms show up. But aspirin et al. do lots of other things, too – some good, some bad. The new findings suggest a compound carefully tailored to block this receptor and do nothing else might be a weapon in the anti-Alzheimer’s arsenal.
Previously: Another big step toward building a better aspirin tablet, Untangling the inflammation/Alzheimer’s connection and Study could lead to new class of stroke drugs
Photo by Henry Markham