Alzheimer’s disease begins at the synapse, the space where neurons connect. The biggest bad guy in this disease is a sticky protein called beta-amyloid. Either too much is made or not enough is cleared away, and as beta-amyloid accumulates, it creates a gooey clog in the synapse, preventing the neurons that meet there from communicating. As a result, the information those neurons carry can’t be transmitted or retrieved. The beta-amyloid “goo” prevents these two neurons from “talking” to each other. We notice this molecular event because we forget something.
When too much beta-amyloid causes the synapse to fail, we begin to see the symptoms of Alzheimer’s. There are many risk factors that can contribute to having too much beta-amyloid. What are these risk factors?
First, let’s imagine a seesaw-style scale and the risk factors, which each vary in weight, are being piled on one arm of the scale. When that arm hits the floor, we have Alzheimer’s.
The biggest risk factor for developing Alzheimer’s is age. For reasons we still don’t entirely understand, as we get older, we accumulate more beta-amyloid. The chances of being diagnosed with Alzheimer’s increase steadily as we age. Right now, the risk of Alzheimer’s doubles every year after the age of 65. About half of people who are 85 and older have Alzheimer’s.
Another risk factor is genetics. There is a rare form of Alzheimer’s called Familial Alzheimer’s, which always begins well before the age of 65 (typically in the 40s and 50s) and runs in families, that is autosomal dominant. This means that a single genetic mutation causes the disease. Picture the seesaw scale again. Genetic mutation is the only risk factor on the scale, and the arm is sitting on the floor.
Scientists have discovered three genetic mutations that cause this early-onset Familial Alzheimer’s. All three of these mutations result in molecular changes that cause an excess of beta-amyloid.
But this type of genetic risk factor is relatively rare, accounting for only about 5% of Alzheimer’s cases. The contribution of genetic risk factors to the development of Alzheimer’s for the vast majority of cases weighs much less on the scale, tipping the arm only a little bit.
For example, ApoE4 is a known genetic risk factor for Alzheimer’s. Forty to 65% of people with Alzheimer’s carry at least one copy of this mutation. But you can have two copies of this mutation (one inherited from each parent) and not have the disease. Again, imagine the arm of the scale tipped a bit with each copy of this mutation, but the arm is still well above the floor. Likewise, you can have zero copies of ApoE4 but have Alzheimer’s. The arm of your scale would be free of ApoE4 but piled high with other risk factors that tipped the scale over, leading to expression of the disease.
3. Head Trauma
Prior experience with head trauma, especially if consciousness was lost, increases the risk of developing Alzheimer’s. Always wear a seat belt and helmets.
In a recent study out of Japan that looked at over 1000 men and women over the age of 60, it was found that people with diabetes (especially type 2) were twice as likely to develop Alzheimer’s. Researchers are now trying to understand the molecular mechanisms that link diabetes to Alzheimer’s. It’s thought that the link may be twofold.
Nerve cells require a lot of energy to do the work of communicating. They get this energy from oxygen and glucose in the blood. With diabetes, cells lose their ability to respond to insulin, the molecule that transports glucose from the blood into the neurons, and so neurons have to cope with less glucose. Diabetes also often leads to damaged blood vessels, which compromises the delivery of oxygen to the nerves in the brain. Neurons already struggling to communicate despite too much beta-amyloid may lose the battle if glucose and oxygen are deprived.
Think of the scale arm with a bunch of risk factors piled on it. It’s hovering above ground but fighting to maintain that position. Things aren’t looking good for that synapse, but it’s still managing to function. Those neurons are still able to talk to each other. We aren’t showing any symptoms of Alzheimer’s yet. Add diabetes, and less oxygen and glucose to provide the energy the neurons need, and the scale arm goes crashing to the ground. Now we have Alzheimer’s.
5. Cardiovascular Disease
Eighty percent of people with Alzheimer's disease also have cardiovascular disease. Scientists are trying to better understand the link between heart health and Alzheimer’s disease, but we do know a few things about this relationship.
Cholesterol drives the production of beta-amyloid. For a brain that is already struggling to keep beta-amyloid levels in check, high cholesterol can be a risk factor that tips the scale. Doctors prescribe statins for people diagnosed with Alzheimer’s to help keep cholesterol levels down.
Again, the neurons in your brain need a lot of oxygen to do their job. If you have high blood pressure and if you have plaques in your blood vessels, your blood vessels are less efficient at delivering this oxygen to your brain. Not enough oxygen can be the weight that tips the Alzheimer’s scale.
All the risk factors for heart disease (things like poor diet, lack of exercise) are also risk factors for Alzheimer’s. And this means that things like a healthy, Mediterranean diet (whole grains, red and purple fruits and vegetables, fish, nuts) and exercise may not only protect the heart, they may protect us from Alzheimer’s. In fact, in animal studies, exercise has been shown to clear beta-amyloid better than any pharmaceutical we know of. Think of diet and exercise as weights on the other arm of the scale.
There is currently no cure for Alzheimer’s, but understanding these risk factors offers us some good news. While we can’t do anything about getting older or the genes we’ve inherited from our parents, eating smart, keeping cholesterol levels and blood sugar low, exercising, wearing a helmet when bicycling or skiing, and wearing a seat belt in the car are among the things we can do to keep the arm of the Alzheimer’s scale from tipping to the ground.