What Causes Alzheimer’s

Many people have had some personal experience with Alzheimer's disease through friends or family. In early stages, it can show up as lapses in memory, which often progresses to affect a person's ability to recognize their loved ones, and think, act, or respond to the environment around them.

But what exactly is Alzheimer's, and what happens in the brain to cause cognitive decline?

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Amyloid Plaques and Tau Tangles

More than 1 in 10 Americans over the age of 65 (about 7 million people) are living with Alzheimer's disease or some other form of dementia. By the year 2050, that number is projected to almost double, increasing the cost of care to around $1 trillion.

There are many types of dementia. Alzheimer's is the most common, accounting for 60-80% of cases, according to the CDC. Alzheimer's happens when brain cells stop working properly, particularly neurons, the nerve cells that make possible everything we do, from thinking to walking, talking and eating. The reasons the neurons break down are still being investigated, but the most prominent theory has to do with two proteins: amyloid and tau.

Sarah A. Kremen, MD

Amyloid builds up outside the brain's neurons. Surprisingly, science still hasn't identified its purpose. According to Sarah Kremen, MD, director of the Goldrich Clinical Trials Program, researchers think it might have a protective function. But as people age, amyloid particles start to clump together and form deposits called plaques. As the plaques build up in the brain, the theory is that they become an irritant to other cells and proteins, in particular the protein called tau.

"Neurons have a kind of skeletal structure," explained Kremen. "The tau helps hold the structure together. When the tau gets irritated, it misfolds and the neuron becomes misshapen and can't function well. That leads to a decreased ability to communicate with the other neurons around it. And it's bad communication between neurons that causes the cognitive and behavioral changes we see in people with Alzheimer's."

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Beyond Amyloid and Tau

New treatments help remove amyloid from the brain. But they have limited effectiveness in relieving symptoms or slowing down disease progression. So researchers continue to look for other causes of Alzheimer's. And over the last few years, they've identified many other possible contributors to the disease, including inflammation and vascular disease (diseases involving blood vessels, arteries and veins).

"Even people with a pretty heavy burden of amyloid may not develop memory symptoms, and the thinking is that amyloid alone is not enough, that there has to be a vascular component as well," said Zaldy Tan, MD, director of the Bernard & Maxine Platzer Lynn Family Memory and Aging Program and Medical Director of the Jona Goldrich Center for Alzheimer's and Memory Disorders. "If you have a stroke or chronic high cholesterol or uncontrolled high blood pressure, that can damage tiny blood vessels in the brain called capillaries and cause disruptions in blood supply. And these may cause damage to neurons and axons, which are like the tails that neurons use to transmit information."

One recent study found that large fat-protein complexes in the blood can also cause inflammation and damage to capillaries.

Another possible source of inflammation in the brain comes from cells called microglia. "Microglia are the brain's immune cells," explained Kremen. "They act like white blood cells to protect the brain. As people age, it's thought that amyloid or something else causes these microglia to overreact and cause inflammation that can harm surrounding cells."

"You could write an entire book on the possible causes of cognitive decline," Tan said. "Ultimately, it's the combination of risk factors in an individual who is genetically susceptible that result in Alzheimer's disease."

Read: Am I at Risk for Dementia? What You Need to Know

Zaldy S. Tan, MD, MPH

Risk Factors

Here are some of the risk factors associated with Alzheimer's.

• High blood pressure after the age of 40
• High cholesterol after the age of 40
• Obesity
• Diabetes
• Lack of exercise
• Lack of sleep or poor sleep quality
• Excessive alcohol consumption
• Smoking and secondhand smoke
• Air pollution
• Traumatic brain injury
• Depression
• Lower levels of education
• Social isolation
• Untreated hearing loss
• Untreated vision loss

There's also a genetic component. People with a copy of the gene APOE4 have been found to be at greater risk for cognitive decline and at an earlier age. People with two copies of the gene are at an even greater risk.

A person with any of these risk factors may never develop Alzheimer's, and a person with none of them might. But doctors agree that reducing these risk factors will improve the chances of avoiding the disease, or at least staying healthier longer.

Early detection is important for any effort to treat or delay the onset of the disease. If you or someone you care about is exhibiting symptoms that might be attributable to Alzheimer's, talk to a doctor.