Amyloidosis is a condition in which there is a deposition, in many tissues, of an abnormal extracellular fibrillar protein, termed amyloid.
Amyloid is derived from many different precursor peptides, with the precursors themselves often being fragments derived from larger proteins; it is deposited as a meshwork of rigid, straight fibrils that are 10-15 nm in diameter, being composed of the precursor peptides lined up in an antiparallel b-pleated sheet structure.
It is therefore the physical arrangement of the constituent peptides that makes a protein an amyloid, rather than any specific peptide sequence.

Amyloid is detected histologically as a bright-pink hyaline material.
It also takes up certain special stains, with the most widely known being Congo red, with electron microscopy showing it to have a fibrillar ultrastructure.

Despite uncertainty about why amyloid is formed, there are well characterized associations between particular diseases and the deposition of amyloid.
In each case, there is an accumulation of a precursor peptide which is processed into an amyloid protein.

In some of these diseases there is an identifiable reason for the accumulation of the precursor peptide, and the amyloid is termed secondary amyloid.
In other cases, the cause of the accumulation of a precursor peptide is not known, and the amyloid is termed primary amyloid.
In addition, there are several inherited disorders, the heredofamilial amyloidoses.

Amyloid is composed of filaments of protein deposited extracellularly.

Amyloid is deposited outside cells, and can be classified into localized or systemic patterns

Amyloid is deposited in the extracellular compartment of tissues, and in H&E preparation it is seen as a uniformly eosinophilic (pink-staining) material.
It can be highlighted in histological sections by the use of special stains such as Sirius red and Congo red.
Congo red staining is commonly used for diagnostic purposes, with amyloid staining orange, and exhibiting a green coloration when viewed with polarized light.

Amyloidosis may involve many tissues in the body as it is particularly deposited in the blood vessel walls and basement membranes.
The progressive accumulation of amyloid leads to cellular dysfunction, either by preventing the normal processes of diffusion through extracellular tissues, or by the physical compression of functioning parenchymal cells.
In some diseases, amyloidosis is a systemic process affecting many organs simultaneously (systemic amyloid); there is also a group of conditions in which amyloid only affects one organ or tissue (localized amyloid).

Amino-acid sequencing of amyloid proteins in different disease states has enabled a classification of amyloid to be made on biochemical grounds.

The commonest example of amyloid deposition is in the nervous system, in both Alzheimer's disease and normal ageing.
The amyloid is derived from a normal, neuronal membrane protein termed Alzheimer precursor protein (APP), being formed from a peptide fragment termed b-protein or A4 protein.

Amyloid that is associated with an abnormal proliferation of plasma cells is made up of immunoglobulin light chains, with such amyloid deposition occurring in diseases such as myeloma and plasmacytoma.
Reactive amyloid may be associated with long-standing chronic inflammatory processes.
As in any inflammatory disorder, the associated systemic acute-phase response causes excessive production of serum amyloid A protein (a normal, acute phase protein) by the liver. With time, and for uncertain reasons, some of this protein is deposited as amyloid.
Diseases that lead to this type of secondary amyloid include tuberculosis, rheumatoid arthritis, bronchiectasis and chronic osteomyelitis.

Tumours of peptide-secreting endocrine cells may form amyloid from the hormone peptide, e.g. in the calcitonin-derived amyloid in medullary carcinoma of the thyroid.
In Type II diabetes, the excessive secretion of amylin by the b-cells of the pancreas is associated with its deposition as islet amyloid.
Uncommon familial types of amyloid are believed to be caused by gene polymorphisms in normal proteins.
The amino-acid substitutions are believed to make the proteins, or their peptide fragments, susceptible to amyloid formation.

Amyloid is mainly deposited in the kidney, heart, liver, spleen and nerves

The kidneys are the organs most commonly functionally impaired by systemic amyloidosis, usually presenting with proteinuria or the nephrotic syndrome.

Deposition of amyloid in the spleen can occur in either a diffuse pattern or a nodular pattern.

In the liver, amyloid is deposited in the space between the sinusoidal lining cells and the hepatocytes.
Clinically, hepatic amyloidosis may be a cause of hepatomegaly.
However, there is rarely significant clinical evidence of impaired liver function.

Amyloid involvement of the heart may be a manifestation of senile cardiac amyloid, which is derived from transthyretin (pre-albumen).
The most severe form of cardiac amyloid is seen in systemic amyloidosis, causing cardiomyopathy.