A-BETA-AMYLOIDOGENESIS - UNIQUE, OR VARIATION ON A SYSTEMIC THEME

For more than a century amyloid was considered to be an interesting, u nique, but inconsequential pathologic entity that rarely caused signif icant clinical problems. We now recognize that amyloid is not one enti ty. In vivo it is a uniform organization of a disease, or process, spe cific protein co-deposited with a set of common structural components. Amyloid has been implicated in the pathogenesis of diseases affecting millions of patients. These range from Alzheimer's disease, adult-ons et diabetes, consequences of prolonged renal dialysis, to the historic ally recognized systemic forms associated with inflammation and plasma cell disturbances. Strong evidence is emerging that even when deposit ed in local organ sites significant physiologic effects may ensue. Wit h emphasis on A beta amyloid, we review the present definition, classi fication, and general in vivo pathogenetic events believed to be invol ved in the deposition of amyloids. This encompasses the need for an ad equate amyloid precursor protein pool, whether precursor proteolysis i s required prior to deposition, amyloidogenic amino acid sequences, fi brillogenic nucleating particles, and an in vivo microenvironment cond ucive to fibrillogenesis. The latter includes several components that seem to be part of all amyloids. The role these common components may play in amyloid accumulation, why amyloids tend to be associated with basement membranes, and how one may use these findings for anti-amyloi d therapeutic strategies is also examined.