Amyloid is an extracellular, proteinaceous material called
amyloid which is composed of non-branching fibrils organized into a beta-pleated
sheet structure. By light microscopy amyloid appears as an amorphous, homogenous,
pink material that can be stained by Congo red and has apple-green birefringence
under polarized light. Immunofluorescence can be used to detect amyloid
composed of light chains.
There are several forms. The most common in the U.K. is the AL form
of amyloid derived from light chains of immunoglobulin, usually as a result
of increased light chain production from multiple myeloma, and light chains
may also appear in the urine. The AA form of amyloid is derived from serum
amyloid-associated protein and appears in persons with chronic inflammatory
disease conditions such as rheumatoid arthritis or tuberculosis. In both
cases, macrophages probably are involved in processing the amyloid protein,
though it is not clear exactly why amyloid appears.
Two conditions in the brain that are associated with amyloid are:
Alzheimer’s disease: one of the hallmark of this condition is the accumulation
of amyloid plaques between nerve cells (neurons) in the brain. Beta-amyloid
is a fragment of a protein that is snipped from another protein called
amyloid precursor protein (APP). In a healthy brain, these protein fragments
would be broken down and eliminated. In Alzheimer’s disease, the fragments
accumulate to form hard, insoluble plaques. The reason for this is not
known.
Cerebral amyloid angiopathy (CAA) refers to the deposition of ß-amyloid
in the media and adventitia of small- and mid-sized arteries (and less
frequently, veins) of the cerebral cortex and the leptomeninges.CAA can
present as intracranial hemorrhage (ICH), dementia, or transient neurologic
events. ICH is the most consistent effect of CAA.Deposition of amyloid
damages the media and adventitia of cortical and leptomeningeal vessels,
leading to thickening of the basal membrane, stenosis of the vessel lumen,
and fragmentation of the internal elastic lamina. This can result in fibrinoid
necrosis and microaneurysm formation, predisposing to hemorrhage. Some
evidence suggests that the amyloid is produced in the smooth muscle cells
of the tunica media as a response to damage of the vessel wall (perhaps
by arteriosclerosis or hypertension).