Alzheimer's Research Takes a New Turn
Study suggests that gummed-up synapses -- not plaque -- may be at the root of aging brain diseases
WebMD News Archive
By Dennis Thompson
TUESDAY, Aug. 13 (HealthDay News) -- A protein that accumulates in healthy aging brains could prove to be the culprit behind the natural forgetfulness that comes with growing old as well as advanced neurodegenerative diseases such as Alzheimer's, according to a new study.
The protein, known as C1q, accumulates on the brain's synapses as people age, potentially gumming up the works, said Dr. Ben Barres, professor and chair of neurobiology at the Stanford University School of Medicine and senior author of the study, published Aug. 14 in the Journal of Neuroscience.
A post-mortem review of mouse and human brains found that the amount of C1q in the brain increases as much as 300-fold with aging.
By comparing brain tissue from mice of varying ages as well as postmortem samples from a 2-month-old infant and an older person, the researchers found that the growing C1q deposits weren't randomly distributed along nerve cells.
Instead, they heavily concentrate at synapses (the junctions between nerve cells), where they could hamper the conduction of electrical and chemical signals in the brain.
"Synapses are not being lost," Barres said. "However, we see the synapses aren't working so good with all that C1q stuck to them. It's detrimental."
But C1q is known to play an important part in the developing brain during childhood, and Barres suspects that this function could lead the protein to attack the synapses if triggered. Such an attack could be the cause of Alzheimer's disease and other neurodegenerative disorders.
This hypothesis runs counter to prevailing theories about Alzheimer's, which have focused on the accumulation of amyloid plaques in the brain as a cause of the disease.
In a normal developing brain, synapses are both created and destroyed -- a process Barres likens to "pruning" the brain by preserving necessary synapses and eliminating the excess.
"What wasn't clear is what the molecular basis of the synapse pruning was," Barres said. "It involves a normal immune protein that people didn't even realize was in the brain -- C1q."
C1q is capable of clinging to the surface of foreign bodies such as bacteria or to bits of dead or dying human 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.