Updated on February 9, 2024.
Proteins are substances that play many important roles in many important processes throughout the body. The structure of cells, signaling between cells, the transport of substances (like oxygen and nutrients) throughout the body, the body's ability to fight infection, and the production of hormones are all examples of processes that rely on different proteins—and an example of why the body is constantly producing new proteins.
Amyloidosis is a group of diseases that occur when something goes wrong with the formation of proteins.
Amyloids and amyloid deposits
To understand amyloidosis, it helps to understand amyloids. In very basic terms, an amyloid is a cluster of proteins. There are functional amyloids, which are involved in normal processes within the body, such as breaking down infected cells and storing hormones. There are also amyloids that are associated with disease, which are sometimes called pathological amyloids.
Disease-associated amyloids occur when cells produce large numbers of misfolded proteins. ”Folding” is a series of steps in protein formation where a protein is folded into a specific (and complex) shape and structure. Misfolded proteins are created when something goes wrong in this series of steps, creating proteins that are misshapen. Misfolded proteins do not function correctly.
When a person has amyloidosis, these misfolded proteins cluster together and form amyloids. As more amyloids accumulate, they form clumpy masses called aggregates or amyloid deposits. As amyloid deposits increase in size and number, they can interfere with the normal functioning of tissues and organs.
Causes and types of amyloidosis
There are several different types of amyloidosis, which are named based on the misfolded proteins that form the amyloid deposits. Different types of amyloidosis cause amyloid deposits in different organs and tissues—and as a result, cause different symptoms and complications.
Examples of different types of amyloidosis include:
AL Amyloidosis (Light Chain Amyloidosis)
- Formerly known as primary amyloidosis and myeloma-associated amyloidosis, AL amyloidosis involves amyloid deposits made from abnormal antibody proteins called light chains.
- AL amyloidosis overlaps with multiple myeloma and other bone marrow cancers. The cancerous bone marrow cells create large numbers of abnormal light chain proteins, which form amyloid deposits.
- AL amyloidosis can damage many different organs, including the heart, kidneys, nervous system, GI tract, skin, and tongue.
A Amyloidosis (AA)
- Also known as secondary amyloidosis, AA involves abnormal versions of serum amyloid A protein (SAA), which is produced in the liver in response to inflammation.
- AA occurs secondary to chronic inflammatory disorders and infections, including rheumatoid arthritis, Alzheimer disease, inflammatory bowel disease, and tuberculosis. It is also associated with cancers.
- It most often affects the liver, kidneys, and spleen. It can also make treatment of the underlying condition more complicated.
ATTR Amyloidosis (Transthyretin Amyloidosis)
- ATTR amyloidosis involves a protein called transthyretin (TTR), which is made in the liver. It can be classified into several different types. The two main types are hereditary ATTR amyloidosis and wild-type ATTR amyloidosis.
- Hereditary ATTR amyloidosis is caused by a genetic mutation where the body creates abnormal TTR that accumulate and form amyloid deposits. It primarily damages the nervous system and heart, though it can also cause problems with the eyes and other organs.
- Wild-type ATTR amyloidosis involves amyloid deposits that are made from normal (non-mutated) TTR. These amyloid deposits typically form in heart tissue and cause problems with the heart, but it also affects the nervous system in some cases. It tends to occur in people over the age of 65.
In addition to the amyloidosis types outlined above, there are other subtypes. This includes localized amyloidosis, where amyloid deposits are limited to a specific area of the body (such as the airways, skin, eyes, bladder, GI tract, or breasts).
