10 Common Causes of Amyloidosis

2. Hereditary

Hereditary amyloidosis runs in families. You inherit a changed gene from one parent, which causes certain proteins in your body to misfold and form amyloid deposits in your organs. This type follows an autosomal dominant pattern, so you only need one changed gene to develop the condition. If one parent carries the gene, you have a 50 percent chance of inheriting it.

Several gene changes lead to hereditary amyloidosis. The most common form involves transthyretin, a protein your liver makes. When this protein becomes unstable, it builds up in your nerves and heart. This buildup can cause numbness, tingling, weakness, and heart rhythm problems.

Other inherited forms involve proteins such as fibrinogen, apolipoproteins, lysozyme, and gelsolin. These forms often affect specific organs, especially the kidneys. When amyloid collects in your kidneys, you may develop protein in your urine, swelling in your legs, and kidney failure over time.

3. Age-Related Systemic Amyloidosis

Age-related systemic amyloidosis, often called wild-type ATTR amyloidosis, develops as you grow older and usually affects men over age 75. In this type, a normal protein changes shape over time and builds up in your organs. This protein most often collects in your heart, which makes the heart muscle stiff.

You may notice shortness of breath, swelling in your legs, or an irregular heartbeat. Some people develop carpal tunnel syndrome years before heart symptoms appear. Unlike hereditary forms, this type does not result from a gene change but happens slowly with aging.

Doctors use blood tests, heart scans, and a biopsy to confirm the diagnosis. Treatment focuses on managing symptoms and slowing protein buildup. Medicines that support heart function or stabilize the abnormal protein may help prevent deposits.

4. Organ-Specific Amyloidosis

Organ-specific amyloidosis develops when amyloid proteins build up in one main organ instead of spreading through your body. This form can still affect how that organ works but does not usually involve many systems at once. You may develop amyloid deposits in your heart, kidneys, skin, lungs, or bladder.

For example, when amyloid collects in your heart, it can make the heart muscle stiff, which causes shortness of breath, swelling in your legs, or an irregular heartbeat. When it builds up in your kidneys, you may notice swelling in your feet or foamy urine due to protein loss.

In some cases, amyloid forms in your skin and causes firm lumps or patches. If it affects your lungs, you might have a cough or trouble breathing. When limited to the bladder, it can lead to blood in your urine. Long-term inflammation in a single area or certain protein changes that stay confined to one organ may cause this type.

5. Multiple Myelomas

Multiple myeloma is a cancer that starts in plasma cells, which help your body fight infection. When these cells turn cancerous, they grow out of control and crowd out healthy blood cells. This disease can lead to AL amyloidosis, where your body makes abnormal light chains that build up as amyloid in organs such as your heart, kidneys, liver, or nerves.

You may not notice symptoms in the early stages, but over time, you might feel very tired, weak, or short of breath. Bone pain, frequent infections, and weight loss can also occur. Some people learn they have myeloma after routine blood tests show abnormal protein levels.

Your risk increases as you get older. It is rare in people under 45. Men develop it slightly more often than women, and it is more common in people of Black African or African Caribbean background. Doctors treat multiple myeloma with chemotherapy, corticosteroids, targeted therapy, or stem cell transplant to control abnormal plasma cells and reduce harmful protein production.

6. AA Amyloidosis

AA amyloidosis develops when you have long-term inflammation in your body, often linked to chronic diseases that keep your immune system active for many years. This ongoing inflammation leads to a buildup of a protein called serum amyloid A. Your liver makes this protein during inflammation. When inflammation does not stop, the protein changes shape and forms deposits in your organs, often collecting in your kidneys but also affecting your liver, spleen, or digestive tract.

Common causes of long-term inflammation that can lead to AA amyloidosis include rheumatoid arthritis, chronic infections such as tuberculosis, inflammatory bowel diseases, and long-standing autoimmune disorders. You may notice swelling in your legs, fatigue, or weight loss. Kidney damage is common, and you might see foamy urine due to protein loss. Some people do not notice symptoms until organ damage becomes advanced.

7. Immunoglobulin Light Chain Amyloidosis

Immunoglobulin light chain amyloidosis (AL amyloidosis) starts in your bone marrow, where plasma cells produce abnormal light chain proteins. These light chains, part of antibodies, clump together and create amyloid deposits in your heart, kidneys, liver, nerves, or digestive tract.

You may notice symptoms based on the organ involved, such as swelling in your legs or foam in your urine if it affects your kidneys, or shortness of breath, tiredness, or lightheadedness if it affects your heart. Doctors often link AL amyloidosis to blood disorders such as multiple myeloma.

They use blood tests, urine tests, imaging, and sometimes a bone marrow biopsy to confirm the diagnosis. Treatment stops abnormal plasma cells from making more light chains using chemotherapy drugs, targeted therapy, or a stem cell transplant. The goal is to reduce protein buildup and protect your organs from further damage.

8. Gastrointestinal Amyloidosis

Gastrointestinal amyloidosis happens when amyloid protein builds up in your digestive tract, which affects your stomach, intestines, liver, or other nearby organs. You may notice ongoing stomach pain, nausea, or a feeling of fullness after eating small amounts of food.

Some people develop diarrhea, while others have constipation. You might also lose weight without trying or feel very tired because your body cannot absorb nutrients well. If amyloid affects your liver, it can cause swelling or discomfort in the upper right side of your abdomen.

When it involves the intestines, you may see blood in your stool or have trouble digesting food. These symptoms often look like other digestive problems, which can delay diagnosis. Several types of amyloidosis can involve the digestive system, including AL amyloidosis and AA amyloidosis linked to long-term inflammatory diseases.

9. Chronic Inflammatory Diseases and Chronic Infections

Living with a long-term inflammatory disease keeps your immune system active, which can lead to AA amyloidosis as your body makes high levels of a protein during inflammation that builds up in organs. Several chronic inflammatory diseases raise your risk. These include rheumatoid arthritis and inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis. Long-standing lung diseases that cause ongoing inflammation can also increase your risk.

If these conditions stay uncontrolled, your body continues to produce inflammatory proteins, which can collect in your kidneys, liver, or other organs. Chronic infections, such as long-term bone or lung infections and untreated bacterial infections, can also trigger this process by keeping your immune system turned on. Sepsis is a severe response to infection that can damage organs. While sepsis itself is an emergency and not a direct cause of amyloidosis, repeated or ongoing infections increase inflammation in your body.

10. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Other Plasma Cell Disorders

Monoclonal gammopathy of undetermined significance (MGUS) occurs when your body makes an abnormal protein in the blood due to plasma cells in your bone marrow. Plasma cells usually help you fight infection, but in MGUS they produce one extra, abnormal antibody. MGUS becomes more common as you age, especially after age 50.

MGUS is not cancer, and many people do not have symptoms and learn about it after routine blood tests. Each year, about 1 out of 100 people with MGUS develop a related blood cancer or disorder, including multiple myeloma, certain lymph node cancers, or amyloidosis. The risk builds slowly over time, so doctors monitor you with regular blood work.

Abnormal plasma cells can produce light chains, which are small parts of antibodies. These light chains may misfold and collect in organs such as your heart, kidneys, or nerves. Over time, these deposits damage tissue and affect how your organs work.