Major types of amyloidosis

As has been mentioned before different proteins can be deposited as amyloid in various tissues. This deposition can be restricted to one specific site (such as pancreas, brain, larynx) or can be found throughout the body. In the first situation it is called localised amyloidosis and in the latter it is called systemic amyloidosis. Localised amyloid is seen frequently (such as in the brain in Alzheimer's disease and in the pancreas in diabetes mellitus type II. Only the name amyloid is identical, but the localised types of amyloid mentioned above are completely different because of different precursor proteins. There are also different types of systemic amyloidosis.

Apart from the distinction between localised and systemic forms of amyloidosis it is also possible to differentiate between familial and non-familial forms of amyloidosis. However, nowadays it is possible to characterise amyloid in a chemical way.  Chemical classification of amyloid is the current standard. This can be done by a thorough investigation of a piece of tissue (biopsy) to detect which type of protein is the characteristic protein of the amyloid involved. The five most important systemic forms of amyloid that should be distinguished from each other (four acquired and one hereditary) are AA, AL, A2M, and two ATTR types:


  1. Acquired AA amyloidosis, caused by chronic inflammation. Serum amyloid A protein (SAA), an acute phase reactant, is the precursor protein of this type. Proteinuria and loss of renal function are the most prominent clinical characteristics.

  2. Acquired AL amyloidosis, caused by a plasma cell dyscrasia. Precursor protein of this type is a kappa or lambda immunoglobulin light chain. Clinical characteristics of this type are very diverse, such as cardiomyopathy, hepatomegaly, nephrotic syndrome, severe diarrhoea, carpal tunnel syndrome, and neuropathy (peripheral as well as autonomic neuropathy).

  3. Acquired A2M amyloidosis, caused by chronic dialysis because of complete renal failure. Precursor protein of this type is 2-microglobulin because high serum levels are the result of the impossibility to excrete this protein. Clinical characteristics of this type are carpal tunnel syndrome and joint problems (shoulders, wrists, fingers, hips, vertebral column, etc.).

  4. Acquired ATTR amyloidosis, found at high age (especially older than 80 years) in which the normal wild type precursor protein transthyretin (TTR) is the characteristic protein. Clinically characterised by a slowly progressive cardiomyopathy.

  5. Hereditary ATTR amyloidosis, caused by more than 80 autosomal dominant hereditary point mutations of the precursor protein transthyretin (TTR). Clinical characteristics of this type are peripheral and autonomic neuropathy, but also cardiac, renal, and ocular involvement can be seen. 



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Below is a simple overview of the four acquired forms of systemic amyloidosis.




Underlying disease

Clinical picture

AA Serum Amyloid A Chronic inflammation Nephropathy, autonomic neuropathy, enteropathy
AL Kappa, lambda Monoclonal plasma cell dyscrasia Cardiomyopathy, nephropathy, hepatopathy, splenomegaly, arthropathy, CTS, neuropathy, enteropathy, glossomegaly
A2M 2-microglobulin Longstanding dialysis CTS, arthropathy
ATTR Transthyretin Old age Cardiomyopathy


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Beside ATTR amyloidosis other, rarer forms of hereditary systemic amyloidosis can be found. A simplified overview is presented below.


Mutated protein

Clinical presentations of the various mutations

Apolipoprotein A-I Peripheral neuropathy, nephropathy, peptic ulcer, liver failure, cardiomyopathy, dermatopathy, larynx
Apolipoprotein A-II Nephropathy
ABri Dementia
Cystatin C Cerebral bleeding
Fibrinogen A α-chain Nephropathy
Gelsolin Cranial neuropathy, dermatopathy, cornea lattice dystrophy
Lysozyme Nephropathy, sicca syndrome, petechiae of the skin, gastrointestinal bleeding, liver bleeding
Transthyretin Peripheral neuropathy, cardiomyopathy, nephropathy, vitreous opacities
Leukocyte chemotactic factor 2 (LECT2) Nefropathie


And the other way around (Benson MD, AMYLOID 2005; 12:75-85):

Clinical presentations of the various mutations

Mutated protein

Vitreous opacities Transthyretin
Neuropathy Transthyretin, Apolipoprotein A-I (G26R)
Restrictive cardiomyopathy Transthyretin, Apolipoprotein A-I (C-terminaal)
Nefropathy Apolipoprotein A-I, A-II, Fibrinogen A α-chain, Lysozyme, Leukocyte chemotactic factor 2
Hepatopathy Apolipoprotein A-I, Lysozyme
Dermal Apolipoprotein A-I (C-terminaal), Gelsolin, Lysozyme
Laryngeal Apolipoprotein A-I (C-terminaal)
Cornea lattice dystrofy Gelsolin


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