Amyloidosis

Amyloidosis is a group of disorders in which a protein misfolds, sticks to other copies of itself and forms long, insoluble fibrils called amyloid, built largely from stacked beta sheets. The body struggles to break them down, so they collect between cells and push aside normal tissue. Deposits may be systemic, in many organs, or localized, as with the plaques in the brain in Alzheimer's disease.

The protein involved defines the type. In AL amyloidosis, an abnormal clone of plasma cells, sometimes as part of multiple myeloma, overproduces antibody light chains. AA amyloidosis follows years of inflammation, as in rheumatoid arthritis or chronic infections, and comes from a protein the liver makes during inflammation. ATTR amyloidosis comes from transthyretin, a carrier protein in the blood, either an inherited mutant form or the normal protein in older people, mostly men, in whom it stiffens the heart. Symptoms depend on where deposits build up: heart failure and irregular rhythms, swelling and protein loss from kidney damage, numb hands and feet, an enlarged tongue, or easy bruising.

Diagnosis needs a biopsy, often of abdominal fat, in which amyloid stains with Congo red and shines apple green under polarized light; further tests identify the protein. Treatment targets the source, such as chemotherapy against the plasma cells or drugs that stabilize or silence transthyretin.