From arthritis to Alzheimer's disease: current concepts on the pathogenesis of amyloidosis

Abstract

Amyloid is a generic term referring to a group of diverse but specific extracellular protein deposits which all have common morphologic properties, staining characteristics, and x-ray diffraction and infrared spectra. This review considers the new classification of amyloids, based on the underlying peptides forming the protein fibril, and their diversity. The pathogenesis of inflammation-associated amyloid and its relationship to high density lipoprotein metabolism is examined in detail. The lessons learned from models of inflammation-associated amyloid are extended to the other amyloids (e.g., Alzheimer's disease), and potential reasons for the common structural properties of all amyloids are explored.

Amyloid enhancing factor activity is associated with ubiquitin

“…AA Amylold AA amyloid, a ;4 residue peptide with the approximate molecular size of 8.5kD, is generally seen during chronic idiopathic inflammatory conditions , Kisilevsky 1987, or chronic bacterial infections , Mazur 1989. Familial…”

“…These three classes describe conditions in which many organs are involved in amyloidosis. 4) Isolated organ specifie amyloidosis: although AD and OS were considered the most common organ specifie amyloid diseases (Kisilevsky 1987), now there is evidenee that A4 fibrils May also occur in other organs as weil. Endocrine amyloidosis usually involves the specifie gland secreting the amyloidogenic hormone.…”

“…Amyloidosis describes a heterogeneous collection of systemic diseases characterized by the extracellular deposition of 6-pleated amyloid fibrils of great chemical diversity in various organs and tissues (Glenner 1980, Cohen and Connors 1987, Kisilevsky 1987. Structural studies on purified amyloid proteins indicate at least 10 different chemical forms of human amyloids (Cohen and Connors 1987, Kisilevsky (987).…”

“…Despite significant diversities in the primary structure of amyloid proteins, ail amyloids share a number of distinct staining, spectral and ultrastructural characteristics (Glenner 1980, Cohen and Connors 1987, Kisilevsky 1987). Whether or not various amyloids which develop in response to apparently disparate clinical settings, ranging from rheumatoid arthritis to Alzheimer's disease, share a common pathogenetic link remains a matter of much speculation and intense interest (Glenner 1980, Cohen and Connors 1987, Kisilevsky 1987, Hoffman et al 1984, Glenner and Wong 1984a, Varga et al 1986, Ali-Khan et al 1988b.…”

“…Whether or not various amyloids which develop in response to apparently disparate clinical settings, ranging from rheumatoid arthritis to Alzheimer's disease, share a common pathogenetic link remains a matter of much speculation and intense interest (Glenner 1980, Cohen and Connors 1987, Kisilevsky 1987, Hoffman et al 1984, Glenner and Wong 1984a, Varga et al 1986, Ali-Khan et al 1988b. Hall et al, to our knowledge, were the first to propose stress as the cardinal amyloid inducing factor in mice (Hall et al 1960).…”