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An Ultrastructural Study of Amyloid Intermediates in Aβ 1–42 Fibrillogenesis
Author(s) -
Mads Nybo,
Svehag,
Holm Nielsen
Publication year - 1999
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1999.00526.x
Subject(s) - fibrillogenesis , fibril , chemistry , biophysics , ultrastructure , amyloid (mycology) , amyloid fibril , crystallography , electron microscope , biochemistry , amyloid β , biology , anatomy , pathology , medicine , inorganic chemistry , physics , disease , optics
Many attempts have been made to define early stages and intermediates in amyloid fibrillogenesis that may be susceptible to inhibition. We have developed an in vitro system, based on the use of Aβ 1–42 peptides, in which the development of prestages of protofilaments and protofilament and fibril formation could, for the first time, be followed by electron microscopy, supported by fluorescence spectrometry. The first recognizable ultrastructures after incubation of Aβ 1–42 peptides at 37 °C were globular subunits (4–5 nm in diameter) that gradually became organized into short protofilaments (30–100 nm), which in turn formed fibrils mainly by lateral association. At this stage, part of the protofilaments were seen first as collaterals protruding from the fibrils and then, as they were gradually incorporated, as buds on the fibril surface. A continuous growth of Aβ 1–42 fibrils was observed, seemingly originating from a nucleus, which appeared to consist of aggregates of amyloid intermediates. That protofilaments are intermediates also in the in vivo formation of amyloid was supported by the finding that AL fibrils isolated from amyloid tissues also exhibited radiating protofilaments. The demonstrated globular subunits and early formed protofilaments may be attractive targets for inhibition of fibril formation.