What causes amyloid proteins to accumulate in the body?

Question

Hi doctor,

My uncle is 67 years old and was recently diagnosed with amyloidosis after experiencing fatigue, weight loss, and swelling in his legs and abdomen. The doctors explained that this rare disease involves abnormal protein deposits building up in his organs, but I am still confused about many aspects of his condition. Could you provide me with a detailed overview of what exactly amyloidosis is, the specific type affecting my uncle, and what may have caused the amyloid proteins to misfold and accumulate in his body?

Kindly assist.

Answer 1

Hello,

Welcome to icliniq.com.

Amyloid fibrils are protein polymers comprising identical monomer units (homopolymers). Functional amyloids play a beneficial role in a variety of physiologic processes (for example, long-term memory formation, gradual release of stored peptide hormones). Amyloidosis results from the accumulation of pathogenic amyloids- most of which are aggregates of misfolded proteins in a variety of tissues.

Many mechanisms of protein function contribute to amyloidogenesis, including “non-physiologic proteolysis, defective or absent physiologic proteolysis, mutations involving changes in thermodynamic or kinetic properties, and pathways that are yet to be defined.”

Your uncle is probably suffering from AL-type, systemic amyloidosis. Non-specific systemic symptoms, including fatigue and unintentional weight loss, are common in patients with AL amyloidosis.

Hepatomegaly, with elevated liver enzyme levels – Hepatomegaly with or without splenomegaly is present in a subset of patients, although the frequency is not well defined. A cholestatic pattern with elevated liver enzymes is seen in approximately 25 percent.

In some types of amyloidosis (for example, always in AA, often in AL and ATTR), the amyloid precursors undergo proteolysis, which may enhance folding into an amyloidogenic structural intermediate. In addition, some of the amyloidoses may have a normal proteolytic process that is disturbed, yielding a high concentration of an amyloidogenic intermediate. For example, it was shown that the mast cells of allergic responses may also participate in the development of secondary or amyloid AA in chronic inflammatory conditions. Mast cells hasten the partial degradation of the SAA protein that can produce highly amyloidogenic N-terminal fragments of SAA. However, factors that lead to different organ tropisms for the different amyloidoses are still largely unknown.

I hope this helps you.

Thank you.