Under polarised light, the proteins behind amyloidosis glow apple-green
Amyloidosis happens when proteins fold the wrong way, stack into rigid fibres and pile up in organs the body cannot clean. Its early signs are vague, like tiredness, swollen ankles and breathlessness, so diagnosis often drags on. Doctors confirm it by staining tissue with Congo red and watching it turn apple-green.
Amyloidosis is a family of diseases, not one. There are about 36 types, each caused by a specific protein misfolding; some stay localised while others spread through the body. The common systemic forms are light chain (AL), inflammation-related (AA), a dialysis-related type, and transthyretin disease (ATTR), which can be inherited or simply arrive with old age. Roughly a third of amyloid disease is hereditary and tends to start early, while about half is sporadic and appears late in life, possibly as protein quality control declines with age.
The trouble lies in shape. Misfolded proteins lock together into fibrils built from beta sheets, a structure that resists the enzymes that normally break proteins down, so the deposits accumulate outside cells. Both the finished fibrils and smaller intermediate clumps can poison cells. The kidneys and heart bear the brunt: kidney deposits leak protein into urine, and heart deposits stiffen the muscle. About 20 percent of people with AL disease, and 40 to 60 percent with AA, eventually need dialysis.
Clues can be oddly specific. A fifth of AL patients develop an enlarged tongue, which never happens in the ATTR or AA forms, and fragile vessels can produce bruising around the eyes nicknamed raccoon eyes. Carpal tunnel syndrome in both wrists and lumbar spinal stenosis can hint at wild-type ATTR. A biopsy of belly fat is the usual first test; a negative result does not rule the disease out, and laser microdissection with mass spectrometry is the most reliable way to pin down the type.
AL amyloidosis affects about 3 to 13 people per million each year, usually starting at 55 to 60, and untreated survival ranges from six months to four years. Treatment aims to cut production of the offending protein. The condition has been described since at least 1639, yet it remains overlooked: a 2025 review of 41 major myeloma drug trials found none actively screened participants for it.
Source: Amyloidosis
