How is amyloidosis classified biochemically?

Updated: Nov 12, 2018
  • Author: Robert O Holmes, Jr, DO; Chief Editor: Herbert S Diamond, MD  more...
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Answer

Answer

Amyloid is now classified chemically. The amyloidoses are referred to with a capital A (for amyloid) followed by an abbreviation for the fibril protein. For example, in most cases formerly called primary amyloidosis and in myeloma-associated amyloidosis, the fibril protein is an immunoglobulin light chain or light chain fragment (abbreviated L); thus, patients with these amyloidoses are now said to have light chain amyloidosis (AL). Names such as AL describe the protein (light chain), but not necessarily the clinical phenotype. [5]

Similarly, in most cases previously termed senile cardiac amyloidosis and in many cases previously termed familial amyloid polyneuropathy (FAP), the fibrils consist of the transport protein transthyretin (TTR); these diseases are now collectively termed ATTR.

Proteins that form amyloid fibrils differ in size, function, amino acid sequence, and native structure but become insoluble aggregates that are similar in structure and properties. Protein misfolding results in the formation of fibrils that show a common beta-sheet pattern on x-ray diffraction.

In theory, misfolded amyloid proteins can be attributed to infectious sources (prions), de novo gene mutations, errors in transcription, errors in translation, errors in post-translational modification, or protein transport. For example, in ATTR, 100 different points of single mutations, double mutations, or deletions in the TTR gene and several different phenotypes of FAP have been documented. [7] Twenty-three different fibril proteins are described in human amyloidosis, with variable clinical features.

The major types of human amyloid are outlined and discussed individually in the table below. Great importance is now placed on appropriate and timely typing and classification of each type of amyloid-related disease, to focus therapy and plan appropriate monitoring. [8] The common clinical amyloid entities are AL, AA, ATTR, and Aβ2M types. [8]

Table. Human Amyloidoses (Open Table in a new window)

Type

Fibril Protein

Main Clinical Settings

Systemic

Immunoglobulin light chains

Plasma cell disorders

Transthyretin

Familial amyloidosis, senile cardiac amyloidosis

A amyloidosis

Inflammation-associated amyloidosis, familial Mediterranean fever

Beta2 -microglobulin

Dialysis-associated amyloidosis

Immunoglobulin heavy chains

Systemic amyloidosis

Hereditary

Fibrinogen alpha chain

Familial systemic amyloidosis

Apolipoprotein AI

Familial systemic amyloidosis

Apolipoprotein AII

Familial systemic amyloidosis

Lysozyme

Familial systemic amyloidosis

Central nervous system

Beta protein precursor

Alzheimer syndrome, Down syndrome, hereditary cerebral hemorrhage with amyloidosis (Dutch)

Prion protein

Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia, kuru

Cystatin C

Hereditary cerebral hemorrhage with amyloidosis (Icelandic)

ABri precursor protein

Familial dementia (British)

ADan precursor protein

Familial dementia (Danish)

Ocular

Gelsolin

Familial amyloidosis (Finnish)

Lactoferrin

Familial corneal amyloidosis

Keratoepithelin

Familial corneal dystrophies

Localized

Calcitonin

Medullary thyroid carcinoma

Amylin*

Insulinoma, type 2 diabetes

Atrial natriuretic factor amyloidosis

Isolated atrial amyloidosis

Prolactin

Pituitary amyloid

Keratin

Cutaneous amyloidosis

Medin

Aortic amyloidosis in elderly people

*Islet amyloid polypeptide amyloidosis.


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