APOLIPOPROTEIN-E INCREASES THE FIBRILLOGENIC POTENTIAL OF SYNTHETIC PEPTIDES DERIVED FROM ALZHEIMERS, GELSOLIN AND AA AMYLOIDS

Apolipoprotein E (apoE) has been found in association with several dif ferents types of systemic and cerebral amyloid deposits and the presen ce of the epsilon 4 allele constitutes a risk factor for Alzheimer's d isease. It has been shown that apoE binds and promotes the fibrillogen esis in vitro of Alzheimer's amyloid beta-peptide, suggesting an impor tant role for apoE in the modulation of amyloidogenesis, Due to the co -localization of apoE with several biochemically distinct amyloid depo sits, it has been proposed that apoE plays a general role modulating a nd/or participating in amyloidosis, In the present study, we show for the first time that apoE, isolated from human plasma, increases fibril formation of synthetic peptides comprising the amyloidogenic sequence s of gelsolin amyloid related to familial amyloidosis Finnish type, an d amyloid A found in secondary amyloidosis and familial Mediterranean fever. Our results suggest that apoE acts as a general pathological ch aperone in various amyloidoses by enhancing the transition from solubl e peptides into amyloid-forming, pathological molecules.