Apolipoprotein E increases the fibrillogenic potential of synthetic peptides derived from Alzheimer's, Gelsolin and AA amyloids

FEBS Letters

Asok Kumar, R.¹  Baumann, Marc¹  Castaño, Eduardo M.¹  Prelli, Frances¹  Soto, Claudio² 

[1] Department of Pathology, New York University Medical Center, 550 First Avenue New York, NY 10016, USA;Department of Neurology, New York University Medical Center, 550 First Avenue New York, NY 10016, USA

关键词: Apolipoprotein E;    Amyloidogenic conformation;    Amyloidosis;    Alzheimer's disease;    Pathological chaperone;    apoE;    apolipoprotein E;    AD;    Alzheimer's disease;    Aβ;    amyloid-β peptide;    AA;    amyloid A;    AGel;    gelsolin amyloid;    FAF;    familial amyloidosis of Finnish type;    ThT;    thioflavine T;   

DOI  :  10.1016/0014-5793(95)00863-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Apolipoprotein E (apoE) has been found in association with several differents types of systemic and cerebral amyloid deposits and the presence of the ϵ4 allele constitutes a risk factor for Alzheimer's disease. It has been shown that apoE binds and promotes the fibrillogenesis in vitro of Alzheimer's amyloid β-peptide, suggesting an important role for apoE in the modulation of amyloidogenesis. Due to the co-localization of apoE with several biochemically distinct amyloid deposits, it has been proposed that apoE plays a general role modulating and/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 sequences of gelsolin amyloid related to familial amyloidosis Finnish type, and amyloid A found in secondary amyloidosis and familial Mediterranean fever. Our results suggest that apoE acts as a general pathological chaperone in various amyloidoses by enhancing the transition from soluble peptides into amyloid-forming, pathological molecules.

【 授权许可】

Unknown