Amyloidosis

Proteins are one of the major types of molecules that make up cells and organisms. They carry out many of life’s activities and functions. We continuously make, modify and remove thousands of different proteins to carry out specific jobs. Proteins rely on their 3D structures to function, but sometimes they can lose their shapes, a process called misfolding. If there are enough misfolded molecules of a particular protein, they can stick together and precipitate out of solution to form structures called amyloid fibrils. These fibrils can accumulate in tissues and organs and eventually cause amyloidosis, a group of progressive and often mostly diseases that are eventually fatal. Each type of amyloidosis is caused by a different protein.

Amyloidosis is usually divided into two groups: in systemic amyloidosis, fibrils form throughout the body, whereas in localized amyloidosis, fibrils are restricted to a particular tissue or organ. The best-known example of amyloidosis is Alzheimer’s disease, where fibrils are localized to the brain, causing neurodegeneration. Systemic amyloidosis is generally thought of as less common, but its frequency increases with age and recent studies estimate that most elderly people have some evidence of amyloid fibrils. We don’t know whether these fibrils cause damage, but amyloid can contribute to heart disease or other problems associated with ageing.

In some people, however, aggregation is accelerated and disease occurs earlier in life. This can be caused by an inherited genetic variant that increases the risk of disease, or by a “sporadic” condition that leads to increased production or misfolding of the precursor protein. The most common example of an inherited amyloidosis is caused by variants of the transthyretin gene, which codes for a protein that transports hormones in the blood. This is called “ATTR amyloidosis”. The most common sporadic amyloidosis is caused by antibody light chains secreted from abnormally proliferating plasma cells. This is called “AL amyloidosis”. These diseases are rare, but are increasingly commonly diagnosed as people are living longer and there is more awareness of amyloidosis.