Amyloidosis: History, Pathophysiology and Classification of a not Quite so Rare Disease

Abstract

Even today amyloidosis is an odd and someway mysterious term for most physicians. Actually we should speak of “Amyloidoses” rather than amyloidosis to indicate a group of protein conformational diseases caused by mis-folding and further aggregation of autologous proteins into amyloid fibrils that deposit into organs and tissues. Now more than 30 different proteins have been identified as possible precursors of amyloid fibrils. Regardless of the different precursor protein the misfolding and aggregation process is the same for all the proteins. Here we describe the major mechanisms that lead to fibril formation and eventually cause tissue damage. Finally we elucidate the present classification criteria and differentiate between systemic and localized forms, among which there is Alzheimer's disease. Conversely, major systemic clinical forms are light chain amyloidosis (AL), reactive amyloidosis (AA) and hereditary amyloidosis of which Transthyretin (TTR) is the most common one. TTR molecule however, even in its wild form (TTRwt), may give rise in older people to amyloid fibrils causing senile systemic amyloidosis (SSA). Kidney is involved in AL, AA and many hereditary forms with the exception of TTR, in which its involvement is extremely rare. Clinical signs of renal amyloidosis largely vary from nephrotic syndrome to different degrees of renal failure according to involvement of different renal anatomical structures.