AGING
August 15, 2013

Surprising Culprit in Alzheimer's

This protein protects the brain. But when it builds up, it sets the stage for a disaster that destroys synapses "Like a fire burning through the brain."

Alzheimer’s disease affects 5.4 million Americans, a number expected to triple by 2050. In some people brain cells become clogged with memory-robbing beta-amyloid in their old age, while others remain perfectly fine.

There are many theories why the brain is more susceptible to degeneration and shrinkage as it ages. Now a new study points to the role of an unlikely source as a possible initiator of the widespread destruction of brain cells so pronounced in Alzheimer’s disease and other neurodegenerative diseases: the immune system.

When the researchers compared C1q levels in a young human brain vs. an old brain, they found that it accumulated at synapses in the areas of the brain most vulnerable to Alzheimer’s and Parkinson’s disease

Researchers at Stanford University discovered that a protein called C1q, a protein that plays a key role in the initiation of the brain’s immune response, accumulates abnormally in elderly animals and human subjects. The protein increases approximately 300-fold in the brains of 2-year-old mice — an age equivalent to 70-80 years old in humans.

C1q is one of the first among a 20-member team of proteins called the complement system that is responsible for triggering the body’s immune response. It clings to the surface of foreign invaders such as bacteria or other debris, starting a series of reactions, called the complement cascade, that eventually results in the destruction of the foreign invader.

Immune cells within the brain called microglia release C1q. This occurs rapidly when a foreign substance is detected within the brain tissue. However, the Stanford researchers discovered that in the normal aging brain C1q release does not just occur when an invader is present.

The scientists also discovered that C1q was not distributed randomly; it is heavily concentrated at synapses, the contact points between two nerve cells that are necessary for cell-to-cell communication. The weakening and destruction of synapses is considered one of the main causes of the symptoms of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

When the researchers compared C1q levels in a young human brain vs. an old brain, they found that it accumulated at synapses in the areas of the brain most vulnerable to Alzheimer’s and Parkinson’s disease — the hippocampus and substantia nigra. However, if the C1q protein accumulates in all aging brains, why do some old people develop Alzheimer’s and Parkinson’s while others do not?

The answer, according to the researchers, is that C1q accumulation does not destroy the synapse itself, but leaves it on the brink of destruction. Another event, such as a tiny stroke or a bad infection, will set off the rest of the complement cascade and ensure synapse destruction.

The synapse destruction that results is, “like a fire burning through the brain,” said Ben Barres, chairman of the neurobiology department at Stanford University and senior author of the study in a statement.

…[O]ur findings here suggest that activation of the complement cascade is driving synapse loss, not the other way around.

This causal relationship between the body’s own immune system and synapse destruction goes against the thinking of many previous scientists who thought that synapse loss triggered inflammation — not the other way around.

But the selective vulnerability of aged brain cells due to the accumulation of C1q could explain why people do not get diseases like Alzheimer’s or Parkinson’s until they are older. Activation of the complement system, which is beneficial in fighting foreign invaders, may be detrimental for older people who are trying to stave off dementia.

“Kids don’t get Alzheimer’s or Parkinsons…our findings here suggest that activation of the complement cascade is driving synapse loss, not the other way around,” Barres said.

The study is published in the Journal of Neuroscience.
COMMENTS
NOTE: We regret that we cannot answer personal medical questions.
 
FOLLOW US
© 2016 interMDnet Corporation.