Amyloidosis causes are explained by world’s leading amyloidosis diagnosis and treatment expert. How amyloidosis is related to multiple myeloma, a form of leukemia? The problem with the diagnosis of amyloidosis is that the manifestations are so varied. Dr. Anton Titov, MD. Amyloidosis symptoms can mimic many other diseases. A doctor may not think of amyloidosis. A physician may not do the correct diagnostic test. Professor Dr. Mark Pepys, MD. The correct diagnostic test in amyloidosis is a biopsy. Then a physician looks at it under the microscope. It is best to refer the patient to us. We can do our imaging diagnostic procedures. Dr. Anton Titov, MD. It is very difficult to make the diagnosis of amyloidosis. The main problem is to think of the correct diagnosis. You mentioned a celebrity individual. His diagnosis of multiple myeloma might not have been very far from the correct diagnosis. Because multiple myeloma is part of a group of diseases called monoclonal gammopathy. Multiple myeloma is a malignant cancerous disease. But the same cells that are cancerous in myeloma can also cause amyloidosis. Professor Dr. Mark Pepys, MD. Multiple myeloma itself can cause amyloidosis. Similar cells or the same cells can cause amyloidosis. In fact, the commonest type of systemic amyloidosis is caused by these cells. The cells themselves are not cancerous. They don't replicate out of control. They don't invade anywhere else. Dr. Anton Titov, MD. These cells don't damage the local organs where they are. Cells just produce an abnormal protein. It forms the amyloid deposits. Professor Dr. Mark Pepys, MD. The key thing that is happening in amyloidosis is the formation of amyloid. You have normally soluble proteins. For example, egg white. It is true and translucent when the protein is soluble. Then you fry your egg or boil it. Egg white becomes insoluble, hard and white, and opaque. Dr. Anton Titov, MD. So proteins can be in different physical states. There are about 30 different proteins in the body that normally soluble. They can misfold (fold incorrectly) and become abnormal. Insoluble proteins deposit as amyloid fibrils. There are aggregates, clumps of these proteins. They have undergone a change in their physical form. They become insoluble. They lay themselves down in the tissues of the body. The mystery is not why this happens. Because now we understand that in recent years rather well. We understand the physical and biophysical processes of amyloid fibril formation. The big mystery is why doesn't the body get rid of abnormal proteins? Normally the body is extremely efficient at getting rid of abnormal debris. Sometimes you break your leg. Professor Dr. Mark Pepys, MD. You perhaps fell off your bicycle. You have a pint or two of blood in your leg and broken bones. As long as you don't get infected, the body heals it all up very well. Everything gets remodeled and returned to its normal anatomy. Blood clots get removed. The bruising goes away. If you have a bruise. Nothing terrible happens. It all clinically silently fades away. Because there are special cells in the body. They are called macrophages. Macrophages are very competent at recognizing abnormal debris. They clear debris away. The mystery is this. Dr. Anton Titov, MD. Why do they not remove amyloid deposit? These are debris that are made of the body's own proteins. Debris are not made of anything abnormal from the outside. It is just the normal proteins in an abnormal form. That is a big mystery. Professor Dr. Mark Pepys, MD. Nobody has solved this mystery. But that is been my key interest in treating amyloidosis now for many many years. I am trying to understand why that failure of clearance exists. I am trying to remedy it with therapeutic interventions. We are now reasonably well on the way to treat amyloidosis successfully.