Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various other neurodegenerative diseases.
The name amyloid comes from the early mistaken identification of the substance as starch (amylum in Latin), based on crude iodine-staining techniques. For a period, the scientific community debated whether or not amyloid deposits were fatty deposits or carbohydrate deposits until it was finally resolved that it was neither, but rather a deposition of proteinaceous mass.
The remainder of this article will use the biophysical context.
|Alzheimer's disease||Beta amyloid|
|Type 2 diabetes mellitus||IAPP (Amylin)|
|Transmissible spongiform encephalopathy e.g. Bovine Spongiform Encephalopathy aka "Mad Cow Disease"||Prion|
|Medullary carcinoma of the thyroid||Calcitonin|
|Cardiac arrhythmias||Atrial natriuretic factor|
|Rheumatoid arthritis||Serum amyloid A|
|Aortic medial amyloid||Medin|
|Familial amyloid polyneuropathy||Transthyretin|
|Hereditary non-neuropathic systemic amyloidosis||Lysozyme|
|Dialysis related amyloidosis||Beta 2 microglobulin|
|Lattice corneal dystrophy||Keratoepithelin|
|Cerebral amyloid angiopathy||Beta amyloid|
|Cerebral amyloid angiopathy (Icelandic type)||Cystatin|
|systemic AL amyloidosis||Immunoglobulin light chain AL|
|Yeast Prions [Sup35], Rnq1 (parastitic type infection in yeast). There is, in fact, no pathology associated with any yeast prion. The notion of pathology arises because the effect of one of the prion-bearing conditions mentioned ([PSI+]) is a demonstrable defect in the mechanism of protein synthesis. This has no perceptible effect on the vigour or viability of the yeast cells and can only be detected through the presence of particular gene mutations. See below under "Non-disease functional amyloids"|
|Sporadic Inclusion Body Myositis||S-IBM|
Amyloid is characterized by a cross-beta sheet quaternary structure; that is, the beta-strands of the stacked beta-sheets come from different protein monomers and align perpendicular to the axis of the fibril. While amyloid is usually identified using fluorescent dyes, stain polarimetry, circular dichroism, or FTIR (all indirect measurements), the "gold-standard" test to see if a structure contains cross-beta fibres is by placing a sample in an X-ray diffraction beam. There are two characteristic scattering diffraction signals produced at 4.7 and 10 Ångstroms (0.47 nm and 1.0 nm), corresponding to the interstrand and stacking distances in beta sheets. It should be noted that the "stacks" of beta sheet are short and traverse the breadth of the amyloid fibril; the length of the amyloid fibril is built by aligned strands.
Amyloid polymerization (aggregation or non-covalent polymerization) is generally sequence-sensitive, that is, causing mutations in the sequence can prevent self-assembly, especially if the mutation is a beta-sheet breaker, such as proline. For example, humans produce amylin, an amyloidogenic peptide associated with type II diabetes, but in rats and mice prolines are substituted in critical locations and amyloidogenesis does not occur.
There are two broad classes of amyloid-forming polypeptide sequences. Glutamine-rich polypeptides are important in the amyloidogenesis of Yeast and mammalian prions, as well as Huntington's disease. When peptides are in a beta-sheet conformation, particularly when the residues are parallel and in-register (causing alignment), glutamines can brace the structure by forming intrastrand hydrogen bonding between its amide carbonyls and nitrogens. In general, for this class of diseases, toxicity correlates with glutamine content. This has been observed in studies of onset age for Huntington's disease (the longer the polyglutamine sequence, the sooner the symptoms appear), and has been confirmed in a C. elegans model system with engineered polyglutamine peptides.
Other polypeptides and proteins such as amylin and the Alzheimer's beta protein do not have a simple consensus sequence and are thought to operate by hydrophobic association. Among the hydrophobic residues, aromatic amino-acids are found to have the highest amyloidogenic propensity.
For these peptides, cross-polymerization (fibrils of one polypeptide sequence causing other fibrils of another sequence to form) is observed in vitro and possibly in vivo. This phenomenon is important since it would explain interspecies prion propagation and differential rates of prion propagation, as well as a statistical link between Alzheimer's and type 2 diabetes. In general, the more similar the peptide sequence the more efficient cross-polymerization is, though entirely dissimilar sequences can cross-polymerize and highly similar sequences can even be "blockers" which prevent polymerization. Polypeptides will not cross-polymerize their mirror-image counterparts, indicating that the phenomenon involves specific binding and recognition events.
The reasons for amyloid association with disease is unclear. In some cases, the deposits physically disrupt tissue architecture, suggesting disruption of function by some bulk process. An emerging consensus implicates prefibrillar intermediates, rather than mature amyloid fibers, in causing cell death. 
Studies have shown that amyloid deposition is associated with mitochondrial dysfunction and a resulting generation of reactive oxygen species (ROS), which can initiate a signaling pathway leading to apoptosis .
These proteins are typically characterized by their ability to cause aggregation of healthy protein.
Clinically, amyloid diseases are typically identified by a change in the fluorescence intensity of planar aromatic dyes such as thioflavin T or congo red. Congo red positivity remains the gold standard for diagnosis of amyloidosis. This is generally attributed to the environmental change, as these dyes intercalate between beta-strands. Congophilic amyloid plaques generally cause apple-green birefringence when viewed through crossed polarimetric filters. To avoid nonspecific staining, other histology stains, such as the hematoxylin and eosin stain, are used to quench the dyes' activity in other places such as the nucleus where the dye might bind. Modern antibody technology and immunohistochemistry has made specific staining easier, but often this can cause trouble because epitopes can be concealed in the amyloid fold; an amyloid protein structure is generally a different conformation from that which the antibody recognizes.