In a sense, “you” are your synapses. They’re the defining features of the brain circuits that fire up or chill out to generate every thought that passes through your mind and every flicker of emotion or glimmer of recollection you experience. You wouldn’t want to leave home without them.
Some of us get no choice. Massive synapse loss accompanies neurodegenerative diseases from Alzheimer’s to Parkinson’s to multiple sclerosis.
All these disorders are age-related, says Stanford neuroscientist Ben Barres, MD, PhD. “Kids don’t get Alzheimer’s or Parkinson’s,” he told me last week. “And now we think we know why.”
In a study just published in The Journal of Neuroscience, Barres and his colleagues have shown that in perfectly healthy brains, deposits of a protein called C1q gradually build up over time, concentrating at synapses. Interestingly, the first noticeable synaptic C1q deposits appear in the brain centers typically affected early in Alzheimer’s and Parkinson’s.
With advancing age, these deposits spread throughout the brain. By themselves, they don’t seem to impair brain function much. But they may set us up for catastrophic synapse loss.
That’s because C1q is not just any old protein. It’s well known to immunologists as the first batter on a 20-member team of immune-response-triggering proteins collectively called the complement system, as I wrote in my press release announcing Barres’ new study:
C1q is capable of clinging to the surface of foreign bodies such as bacteria or to bits of our own dead or dying cells. This initiates a molecular chain reaction known as the complement cascade. One by one, the system’s other proteins glom on, coating the offending cell or piece of debris. This in turn draws the attention of omnivorous immune cells that gobble up the target … The brain has its own set of immune cells, called microglia, which can secrete C1q. Still other brain cells, called astrocytes, secrete all of C1q’s complement-system “teammates.” The two cell types work analogously to the two tubes of an Epoxy kit, in which one tube contains the resin, the other a catalyst.
Barres has previously shown that in developing brains, which invariably produce a surfeit of synapses, C1q and its complement partner proteins team up to “prune” unused synapses (by flagging them for microglia to gobble up), resulting in more efficient brain architecture. But he suspects the same thing may be happening – inappropriately – in aging brains, where steady C1q accumulation may set the stage for induction of the complement cascade by an astrocyte-inciting incident: say, a head injury, inflammatory infection or series of tiny strokes.
Since, unlike most other cells in the body, nerve cells have no natural defenses against a complement-cascade onslaught, the outcome could be a self-sustaining feeding frenzy of synaptic snacking.
That’s the bad news. The good news: The finding could lead to ways of slowing or stopping the waves of synaptic destruction that characterize neurodegenerative disease.
Previously: Neuroinflammation, microglia, and brain health in the balance, Malfunctioning glia – brain cells that aren’t nerve cells – may contribute big time to ALS and other neurological disorders and Unsung brain-cell population implicated in variety of autism
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