Amyloidosis
Types of amyloidosis
Amyloidosis is not one disease but a family of distinct disorders, each defined by the type of protein that misfolds and the organs it affects. Understanding each type is the first step toward accurate diagnosis and targeted treatment.
01
The wide diversity of amyloidosis
More than 40 human precursor proteins are known to form amyloid deposits. Amyloidosis is classified according to the protein forming the fibrils. The most common systemic forms, AL, ATTR, and AA, each involve different precursor proteins, affect different organ systems, and require fundamentally different treatment strategies.
Because symptoms often mimic those of more common diseases, correct typing is essential and requires specialist testing. Early, accurate typing is the foundation of effective care.
02 · Systemic
AL amyloidosis
AL (light chain) amyloidosis is caused by an abnormal proliferation of plasma cells in the bone marrow that produce misfolded immunoglobulin light chains. These fragments deposit as amyloid fibrils, principally in the heart and kidneys, but potentially in any organ.
It is the most common form of systemic amyloidosis in developed countries. Treatment targets the underlying plasma cell disorder, typically with chemotherapy protocols similar to those used in multiple myeloma.
03 · Systemic
ATTR amyloidosis
ATTR (transthyretin) amyloidosis occurs when the liver-produced transthyretin protein becomes unstable and misfolds. It primarily affects the heart and peripheral nervous system and exists in two distinct forms with different causes and treatment pathways.
Wild-type ATTR
Occurs spontaneously with age, and is not inherited. Most commonly presents as cardiomyopathy in older men. Increasingly recognised thanks to improved cardiac imaging.
Hereditary ATTR
Caused by a genetic mutation in the TTR gene. Inherited in an autosomal dominant pattern. Onset and organ involvement vary by specific mutation; neuropathy is a hallmark feature.
04 · Systemic
AA amyloidosis
AA amyloidosis arises as a secondary complication of persistent systemic inflammation. The culprit protein, serum amyloid A (SAA), is an acute-phase reactant produced by the liver in response to chronic inflammatory states such as rheumatoid arthritis, inflammatory bowel disease, or chronic infections.
The kidneys are the primary target, leading to proteinuria and progressive renal failure. Treatment aims to control the underlying inflammatory or infectious disease and suppress production of serum amyloid A (SAA).
05
Rarer hereditary types
Beyond ATTR, a number of other gene mutations cause rarer hereditary forms of systemic amyloidosis. Each is defined by its precursor protein and carries its own pattern of organ involvement. Genetic testing is essential for diagnosis and has implications for family members.
AAPOA1
Apolipoprotein A-I mutation. Affects kidneys, liver, and peripheral nerves. Autosomal dominant inheritance.
AGEL
Gelsolin mutation. Principally causes cranial neuropathy and corneal lattice dystrophy. Most prevalent in Finland.
ALYS
Lysozyme mutation. Primarily renal involvement with hepatic deposits. British cases historically documented.
AFib
Fibrinogen A-alpha chain mutation. Exclusively renal disease; one of the more common hereditary forms in Western Europe.
06 · Localized
Localized amyloidosis
Unlike systemic forms, localized amyloidosis is confined to a single organ or tissue, most commonly the airways, skin, bladder, or orbit. The amyloid is produced locally by resident plasma cells and does not spread systemically.
Prognosis is generally more favourable than systemic disease, as vital organ function is rarely compromised. Management depends on the site of involvement and the extent of local tissue damage.
07
Compare types
A quick-reference overview of the principal amyloidosis types — protein, primary organs affected, treatment approach, and where to find out more.
| Type | Protein | Primary organs | Treatment approach | Learn more |
|---|---|---|---|---|
| AL | Immunoglobulin light chains | Heart, kidneys, liver, nerves, soft tissues | Plasma cell-directed chemotherapy; stem cell transplant in eligible patients | AL amyloidosis → |
| ATTR — Wild-type | Transthyretin (wild-type) | Heart (cardiomyopathy) | TTR stabilisation and supportive cardiac care; approved indications and availability vary between countries. | wtATTR amyloidosis → |
| ATTR — Hereditary | Transthyretin (mutant) | Peripheral nerves, heart (mutation-dependent) | TTR silencers (siRNA, ASO); stabilisers; liver transplant (select mutations) | hATTR amyloidosis → |
| AA | Serum amyloid A (SAA) | Kidneys, liver, spleen | Control of underlying inflammatory disease; anti-IL-1 agents | AA amyloidosis → |
| Rarer hereditary | ApoA-I, Gelsolin, Lysozyme, Fibrinogen… | Type-dependent (kidneys, nerves, liver) | Supportive; organ transplant in selected cases | Rare hereditary amyloidosis → |