Alzheimer's beta-amyloid peptide is conformationally modified by apolipoprotein E in vitro.
Amyloid beta-peptide (A beta) is a major component of neuritic plaques, a feature of Alzheimer's disease (AD) brains. Recently, we showed that A beta adopts two major conformational states in solution, which differ in their abilities to form amyloid. These are highly amyloidogenic conformer (A beta ac) with a high content of beta-sheet and a slowly amyloidogenic conformer (A beta nac) with a random coil conformation. Apolipoprotein E (apoE), particularly the E4 isoform, which is genetically associated with AD, binds to A beta and modulates fibrillogenesis in vitro. In the present work, the influence of apoE on the conformation of A beta peptides was studied. The results suggest that, under the conditions used, apoE enhances amyloid formation by inducing the conformational transition from A beta nac into A beta ac. We propose that an important step in A beta fibrillogenesis is the transformation induced by apoE of the soluble non-amyloidogenic into the pathological amyloidogenic conformer of A beta.
Soto
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C
Department of Neurology, New York University Medical Center, NY 10016, USA.
Golabek
A
A
Wisniewski
T
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Castaño
E M
EM
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000737:chemistry*; D002942:Circular Dichroism; D006801:Humans; D009454:Neurofibrils / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence
D016229:Amyloid beta-Peptides; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010455:Peptides