The exact causes of amyloidosis are not well understood. This rare condition occurs when abnormal proteins, called amyloids, build up in different organs, leading to a variety of symptoms. Several types of proteins can contribute to amyloidosis, resulting in different forms of the disease. Both genetic and environmental risk factors can play a role in the development of amyloidosis.

How Proteins Become Amyloids

Every cell in the body contains proteins that play vital roles in cell growth, division, and overall function. The cell is constantly making new proteins by creating long chains of amino acids that are then folded into a specific three-dimensional shape.

However, when proteins fold incorrectly, they can clump together in clusters known as amyloid fibrils or amyloid deposits. The body has difficulty breaking down and removing these amyloid proteins, allowing them to accumulate in tissues and organs. Over time, this buildup can cause damage and potentially lead to organ failure.

There are several types of amyloidosis, and each is caused by a different misfolded protein.

• Amyloid light-chain (AL) amyloidosis develops when plasma cells — white blood cells — in the bone marrow produce too much of an antibody protein called immunoglobulin light chain.
• AA amyloidosis occurs when chronic (ongoing) inflammation in the body causes overproduction of the serum amyloid A (SAA) protein.
• Hereditary (familial) amyloidosis is caused by genetic mutations (variations) that result in the production of abnormal proteins.
• Wild-type amyloidosis forms when normally functioning transthyretin (TTR) protein becomes misfolded, although it is not clear why this happens.
• Dialysis-related amyloidosis occurs when the kidneys are damaged and can’t filter out abnormal beta-2 microglobulin proteins, leading to their accumulation.

Read more about the different types of amyloidosis.

Risk Factors for Amyloidosis

It is important to note that while science is good at finding correlations — or apparent relationships — between factors and disease, correlation does not prove the factor causes the disease. Many risk factors for amyloidosis have been identified and are being studied for their role in disease development.

Genetic Factors

Hereditary (or familial) amyloidosis is the only form of the disease caused directly by gene changes. Within this category, there are several subtypes. For example, hereditary ATTR (hATTR) amyloidosis results from a mutation in the TTR gene.

Other subtypes are linked to mutations in genes such as:

• Apolipoprotein A1
• Apolipoprotein A2
• Fibrinogen A alpha chain
• Cystatin C
• LECT2
• Gelsolin

These gene variations are often inherited, but not everyone with a mutation will develop amyloidosis. If you have a family history of the disease — that is, if you have parents, grandparents, or siblings with hereditary amyloidosis — your risk may be higher. Genetic testing can reveal whether you carry these mutations.

If your doctor gives you a diagnosis of hereditary amyloidosis, you may also need to get your genes tested. Tests like urinalyses or biopsies help with diagnosing the overall condition, but they won’t tell you exactly which gene mutations you may have. To sequence your genes, your doctor will need to take a blood sample, which a laboratory can use to “read” the TTR gene or other relevant genes.

If you have a gene mutation connected to amyloidosis, each of your children has a 50 percent chance of getting the gene that causes hereditary amyloidosis if you have it, although they may never develop symptoms.

Age

Amyloidosis risk usually increases with age.

• AL amyloidosis is most often diagnosed in people between 60 and 70 years old.
• AA amyloidosis can affect people at any age but usually occurs in adults.
• People are diagnosed with wild-type ATTR amyloidosis at an average age of 75.

Sex

Men are more likely to be affected by this disease than women, according to Mayo Clinic. About 70 percent of people with AL amyloidosis are men. Men also get the wild-type subtype at higher rates, according to Amyloidosis Foundation. However, both men and women have an equal chance of getting hereditary types, per the National Organization for Rare Disorders (NORD).

Race and Geography

Hereditary amyloidosis is more prevalent in people of certain races or those living in specific areas. In the U.S., this disease is more common in African Americans, according to NORD. Rates of amyloidosis are also higher in Spain, Portugal, Ireland, France, Germany, Sweden, Finland, Greece, and Japan.

Other Health Conditions

Other diseases can sometimes increase a person’s risk of amyloidosis. AA amyloidosis — also called secondary amyloidosis — is always connected to an underlying condition that increases inflammation in the body. For example, rheumatoid arthritis, inflammatory bowel disease (IBD) such as Crohn’s disease or ulcerative colitis, familial Mediterranean fever, and chronic infections can increase the risk of developing AA amyloidosis.

Kidney problems can also lead to amyloidosis. Your kidneys are responsible for filtering out waste that your body doesn’t need. If your kidneys aren’t working properly, they may not be able to eliminate harmful amyloid proteins. Some people with kidney disease also use dialysis treatments to help get rid of waste and toxins. However, dialysis may also be ineffective at removing amyloid deposits. If you have severe kidney problems, you have a greater chance of developing dialysis-related amyloidosis.

Some people with other health conditions also develop amyloidosis. For example, up to 10 percent to 15 percent of people who have AL amyloidosis also have multiple myeloma, a type of blood cancer.

Other conditions that can occur along with amyloidosis include Hodgkin lymphoma, cancer of the thyroid, and Whipple’s disease. However, it’s not always clear whether these other diseases cause amyloidosis.

Can Amyloidosis Be Prevented?

Scientists still don’t understand exactly what causes this disease or why certain proteins can become misfolded. Therefore, there’s nothing specific you can do to prevent amyloidosis. While it’s clear that hereditary forms of amyloidosis are linked to specific gene mutations, you can’t change the genes you are born with.

When some people are diagnosed with amyloidosis, they may worry that certain lifestyle choices caused the disease. However, amyloidosis is not known to be linked to any lifestyle factors. Your risk of amyloidosis is not affected by:

• What you eat, including how much protein you eat
• How stressed you feel
• What you do for a living

It’s not possible to completely prevent AA amyloidosis, but it is possible to lower your risk. This subtype is caused by inflammation, so treating any underlying inflammatory condition may decrease your chances of being diagnosed with AA amyloidosis. If you have an inflammatory condition, it is important to work with your health care team to find treatment options that can keep inflammation under control.

You Are Not Alone With Amyloidosis

On MyAmyloidosisTeam, the social network for those living with amyloidosis, more than 2,000 members come together to discuss life with amyloidosis and share their experiences.

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