Most common late-onset Alzheimer's gene

The most common type of Alzheimer's disease, called late-onset Alzheimer's disease, usually begins after age 65. The most common gene linked to late-onset Alzheimer's disease is a risk gene called apolipoprotein E, also known as APOE.

Genes can have many variations, also called variants. APOE has three common variants:

• APOE e2. This is the least common form of the gene. It reduces the risk of Alzheimer's.
• APOE e4. This form is a little more common. It increases the risk of Alzheimer's. And it's linked to having more-severe Alzheimer's disease.
• APOE e3. This is the most common form of the gene. It doesn't seem to affect the risk of Alzheimer's.

Genes aren't the only factor

Each person inherits two copies of the APOE gene, one from the mother and one from the father. These copies can affect a person’s risk of Alzheimer's. Having at least one APOE e4 variant doubles or triples the risk of getting Alzheimer's disease. Having two APOE e4 variants increases that risk even more. Someone with two APOE e4 variants is 8 to 12 times more likely to develop Alzheimer's disease.

But not everyone who has one or even two APOE e4 variants gets Alzheimer's disease. And many people who don't have an APOE e4 variant get the disease. That suggests that the APOE e4 variant increases the risk of getting Alzheimer's disease but is not a cause. There's likely more to getting Alzheimer's disease than just genes. Lifestyle, race, ethnicity and environment also may contribute.

Other late-onset Alzheimer's genes

Several other genes have been linked to late-onset Alzheimer's disease. Many were identified in large studies, and researchers are investigating their possible roles. Examples include:

• ABCA7. Some forms of this gene seem to be linked to a greater risk of Alzheimer's disease. Researchers suspect that this may have something to do with the gene's role in how the brain uses cholesterol.
• CLU. This gene helps the brain clear out harmful protein fragments called beta-amyloid. Research suggests that an imbalance in the making and clearing of beta-amyloid is key to getting Alzheimer's disease.
• CR1. This gene creates a protein that is active in the immune system. When you don't have enough of this protein, it might cause chronic swelling and irritation, called inflammation, in the brain. Inflammation is another possible factor in getting Alzheimer's disease.
• PICALM. This gene is linked to how brain nerve cells, called neurons, talk to each other. How neurons talk to each other is important for them to work well and to form memories. PICALM also is linked to the making and clearing of beta-amyloid in the brain.
• PLD3. Scientists don't know much about the role of PLD3 in the brain. But it's recently been linked to a significantly increased risk of Alzheimer's disease.
• TREM2. This gene affects how the brain responds to swelling and irritation, called inflammation. Rare variants of this gene are linked to an increased risk of Alzheimer's disease.
• SORL1. This gene plays an important role in beta-amyloid production. Some forms of SORL1 on chromosome 11 appear to be linked to Alzheimer's disease.

As with APOE, variants of these genes are risk factors, not causes. That means that having one of these genetic variants might increase the risk of Alzheimer's. But not everyone with one of these variants will get Alzheimer's disease.

Researchers continue to learn more about Alzheimer's disease. Knowing more about how the disease works might lead to new ways to prevent and treat it.