Amyloidosis Pathogenesis

Hirakura, Y., and Kagan, B. L. (2001). Pore formation by beta-2-microglobulin A mechanism for the pathogenesis of dialysis associated amyloidosis. Amyloid 8, 94-100. 

Since there is growing evidence of the involvement of oxidative and/or nitrative cell damage in the pathogenesis of AD, factors related to lipid peroxidation have been tested as candidate AD biomarkers. Recently, Pratico et al. (Pratico et al., 2002) reported increased levels of isoprostanes (e.g., 8,12-iso-iPF2o,-VI) in body fluids of patients with AD. This finding has been further supported by the elevated levels of this factor in the body fluids of transgenic mice expressing AD amyloidosis (Pratico et al, 2001). 

Most TTR variants are associated with extracellular deposition of amyloid fibrils in various tissue. These autosomal dominant hereditary amyloidoses include amyloidotic cardiomyopathy, familial amyloidotic polyneuropathy, and senile systemic amyloidosis. There is phenotypic variability (e.g., variable age of onset), suggesting that other factors may influence pathogenesis of the diseases. 

Senile Amyloidosis. Senile amyloid protein is found most often in the heart (senile cardiac amyloid), but also in the pancreas and brain. There seems to be an independent pathogenesis for these three forms. Nodular or infiltrative amyloid deposits may also be seen in the skin, lungs, and trachea and may involve endocrine organs such as the pancreas (in long-standing diabetes) or the thyroid (in medullary carcinoma). These forms usually are asymptomatic, except for the cardiac form. 

The discovery of the isoprostanes, recent studies performed in living patients (PraticO et al. 2000), and the development of transgenic animal models of Alzheimer s disease amyloidosis are three important factors helping us to understand and define the role that reactive oxygen species might play in the pathogenesis of this disease (for review see Pra-tic6 2002). 

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