7. What is amyloid? Discuss the mechanisms by which amyloid is 
     deposited in the brain.
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).

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