Ageing and Amyloid Fibrillogenesis: Lessons from Apolipoprotein Al, Transthyretin and Islet Amyloid Polypeptide

The age-associated (or senile) amyloidoses encompass a heterogeneous group of systemic or localized forms of amyloidosis. In this paper we present an overview of three age-associated amyloid forms derived from transthyretin, apolipoprotein AI and islet amyloid polypeptide. Mutations in the respective genes give rise to transthyretin and apolipoprotein AI forms of familial amyloidosis while senile forms of amyloid are associated with the wild-type proteins. Different mechanisms are probably of importance in the fibrillogenesis associated with these three amyloid types. It is also possible that different amyloidogenic pathways exist for a single amyloidogenic protein. Thus, limited proteolysis may be necessary in the fibrillogenesis in senile transthyretin amyloidosis but not in most familial transthyretin amyloidoses. Other factors in the pathogenesis of amyloidosis such as local concentration, nidus formation and glycation are also discussed.