deposit ages. However, this variability of alcian blue and PAS staining once again emphasises the inherent difficulty in recommending a single staining method to identify the material.
As previously noted, the only definitive way to identify amyloid is by its appearance with an electron microscope. Cohen & Calkins and Gueft & Ghidoni described it as extracellular fibres, often in small bundles. Each fibril is 75 Angstroms wide and composed of three linear bands, each 25 Angstroms wide. The fibrils are beaded at 100 Angstrom intervals.
The selectivity of many methods for amyloid appears to depend on two things: hydrogen bonding and the way that its amino acids fold. In most proteins amino acids are folded in a helical manner, rotating around a central point, then deforming the coil as various exposed groups come in contact and influence each other, whether by ionic or non-ionic forces. Amyloid has a different structure, called a beta pleated sheet (β-pleated sheet), which is composed of regular folds like a concertina. This is similar to a sheet of paper folded longitudinally in alternate directions making a zig-zag pattern when viewed on end (see to the right).The dye is often positioned within the creases of the folds, producing a regular alignment of dye molecules (shown in red), much like a crystal would have. This arrangement is referred to as a pseudocrystal, because it causes amyloid to exhibit some of the optical properties of a crystal, such as dichroism and dichroic birefringence. It may also explain the metachromasia with crystal violet.
What causes amyloid
It used to be thought that amyloid was caused by some plasma constituent extruding into the tissues, much like fibrin is formed from fibrinogen in the plasma. Then it was considered to be the results of the reactions between antigens and antibodies which, for some reason, were deposited in the tissues rather than being removed. From the links in the chart below, it appears there may be several causes for the deposition of abnormal proteins as amyloid, including the presence of particular genes. It is not a single substance and there is no single cause for it, but a common thread is that the protein in amyloid is a β-pleated sheet instead of the more usual α-helix. The subject may be investigated by internet searches on the subjects of amyloid, amyloidosis, and the individual amyloid types in the list below. The reader is encouraged to do so as it is a large and quite complicated subject. There is a modern overview at Medscape.
The names of the types of amyloid usually start with the letter "A". The following list of the most common types was made by blending the two lists in the Wikipedia articles referenced below and adding some links. The list is not exhaustive.
|Abbreviation||Amyloid type / gene||Description|
|AL||amyloid light chain||AL amyloidosis / multiple myeloma. Contains immunoglobulin light-chains (λ,κ) derived from plasma cells.|
|AA||SAA||AA amyloidosis, rheumatoid arthritis|
|Aβ||β amyloid / APP||Found in Alzheimer disease brain lesions.|
|Aβ2M||β2 microglobulin||Haemodialysis-associated amyloidosis.|
|ATTR||transthyretin / TTR||Familial amyloid polyneuropathies, senile systemic amyloidosis, leptomeningeal amyloidosis.|
|AIAPP||amylin / IAPP||Pancreatic amyloid in type 2 diabetes.|
|AGel||Gelsolin, GSN||Finnish type amyloidosis.|
|AApoA1||APOA1||Familial visceral amyloidosis, atherosclerosis.|
|AFib||FGA||Familial visceral amyloidosis.|
|ALys||LYZ||Familial visceral amyloidosis.|
|ABri||ITM2B||Cerebral amyloid angiopathy, British-type|
||ITM2B||Cerebral amyloid angiopathy, Danish-type.|
|ACys||CST3||Cerebral amyloid angiopathy, Icelandic-type.|
|AKer||Keratoepithelin||Lattice corneal dystrophy.|
|ACal||Calcitonin||Medullary carcinoma of the thyroid.|
|AANF||atrial natriuretic factor||Senile amyloid of atria of heart, cardiac arrhythmias.|
|AMed||Medin||Aortic medial amyloid.|
|—||OSMR||Primary cutaneous amyloidosis.|
|APrP||Prion protein||Deposits in prion diseases may resemble amyloid, i.e. in Creutzfeldt-Jakob disease, Kuru, BSE, and scrapie.