Immune System Eyed as Cause of Alzheimer's

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Harvard Medical School
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Immune System Eyed as Cause of Alzheimer's

News Review From Harvard Medical School

August 14, 2013

News Review From Harvard Medical School -- Immune System Eyed as Cause of Alzheimer's

A study involving mice has led to a new theory about the cause of Alzheimer's disease. Researchers compared autopsy brain tissue from mice of various ages, a human baby and an older person. They focused on an immune system protein called C1q, which builds up even in healthy brains as they age. Levels of C1q were 300 times as high in older brains as in younger ones. C1q built up mostly at synapses, the junctions between nerve cells. This possibly could get in the way of signals between cells that allow the brain to function. C1q plays a role in the brain in childhood, when some synapses are "pruned" away to allow others to develop. In the immune system, C1q clings to foreign bodies, such as bacteria, or to pieces of dying cells. This sets off a chain reaction. Other proteins build up on top of the C1q. Then other immune system cells gulp down the object. The new study's author thinks that C1q buildup in the brain might trigger such an immune system attack. This could disrupt the connections between cells. The Journal of Neuroscience published the study. HealthDay News wrote about it August 13.


By Howard LeWine, M.D.
Harvard Medical School


What Is the Doctor's Reaction?

We needed a new theory on the cause of Alzheimer's disease. And now we have one.  

For many years, most researchers have focused on beta-amyloid protein as the likely cause of this type of dementia. People with Alzheimer's have more deposits of beta-amyloid around their brain cells than most people. The leading theory says that these deposits gradually destroy synapses in the brain. Synapses are the connections between brain cells and other nerve cells in the body.

The human brain has about 100 billion nerve cells. Each nerve cell has at least 1,000 connections. Multiply those numbers and you get 100 trillion brain synapses. For information to flow rapidly and correctly through the brain, synapses must be healthy enough to send and receive information.

Imagine a railway system with thousands of trains moving at high speeds on tracks that cross each other.  Without perfectly functioning switches, you can imagine the result.

Of course, this analogy is a stretch. Malfunctioning synapses won't cause a brain crash. Here's why: Only a small percentage of synapses are working at any moment in time. And we have trillions of them, and their functions usually overlap.

As we age, we lose function of some synapses. Although we don't yet know the number, losing too many of them leads to loss of memory and thinking.

Researchers at Stanford University School of Medicine suggest that a different protein, rather than beta-amyloid, is directly responsible for destroying synapses. It's called C1q.

During childhood, the developing brain turns synapses on and off to improve brain function. C1q is a normal protein that plays a role in that process.

But that doesn't mean that more C1q is even better. These researchers noticed that with age the brain can build up 300 times more C1q than younger brains.

Perhaps more importantly, the researchers found large amounts of C1q in areas of the brain known to be damaged in people with Alzheimer's and other brain diseases. It's true that most of the researchers' conclusions are based on mice studies. But human autopsy studies of people with Alzheimer's disease show similar C1q patterns.

The researchers suggest that a buildup of C1q in synapses triggers an inflammatory response. And it's the inflammation that destroys the synapses. Perhaps beta-amyloid doesn't cause the inflammation and synapse destruction. Perhaps, instead, the beta-amyloid deposits are a response to the inflammation.  


What Changes Can I Make Now? 

Lifestyle changes can help reduce inflammation. This decreases your risk of dementia. It also improves the health of your heart and blood vessels.  Here are some things you can do to reduce inflammation:

  • Be physically active and dedicate time every day to exercise. Exercise and physical activity count the most in keeping your mind sharp.
  • Eat a Mediterranean-style diet loaded with vegetables and fruits.
  • Maintain a healthy weight.
  • Don't smoke or use other tobacco products. 

You also can take other steps to help preserve memory and thinking as you age:

  • Keep your blood pressure in the normal range.
  • Stay socially engaged with family and friends.
  • Keep your mind active.


What Can I Expect Looking to the Future? 

It's exciting to learn about a new theory for the cause of Alzheimer's disease. You can expect more studies designed to confirm the importance of C1q protein as a potential target for prevention and treatment.


Last updated August 14, 2013

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