Apolipoprotein E increases the fibrillogenic potential of synthetic peptides derived from Alzheimer's, gelsolin and AA amyloids.
Apolipoprotein E (apoE) has been found in association with several different types of systemic and cerebral amyloid deposits and the presence of the epsilon 4 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 beta-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.
Soto
C
C
Department of Neurology, New York University Medical Center, NY 10016, USA.
Castaño
E M
EM
Prelli
F
F
Kumar
R A
RA
Baumann
M
M
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000494:pharmacology*; D018260:Gelsolin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009454:Neurofibrils / Q000187:drug effects* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000737:chemistry / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D001057:Apolipoproteins E; D018260:Gelsolin; D046911:Macromolecular Substances; D010446:Peptide Fragments; D000685:Serum Amyloid A Protein