The Detection of Toxic Amyloid-β Fibril Fragments Through a Surface Plasmon Resonance Immunoassay

Amyloid-β1–42 (Aβ42) forms highly stable and insoluble fibrillar structures, representing
the principal components of the amyloid plaques present in the brain of Alzheimer’s disease (AD)
patients. The involvement of Aβ42 in AD-associated neurodegeneration has also been demonstrated,
in particular for smaller and soluble aggregates (oligomers). Based on these findings and on genetic
evidence, Aβ42 aggregates are considered key players in the pathogenesis of AD and targets for novel
therapies. Different approaches are currently used to detect the various aggregation states of Aβ
peptide, including spectrophotometric methods, imaging techniques, and immunoassays, but all of
these have specific limitations. To overcome them, we have recently exploited the peculiar properties
of surface plasmon resonance (SPR) to develop an immunoassay capable of selectively detecting
monomers and oligomers, discriminating them also from bigger fibrils in a mixture of different
aggregated species, without any manipulation of the solution. In the present study, we extended
these previous studies, showing that the SPR-based immunoassay makes it possible to unveil the
fibril fragmentation induced mechanically, a result difficult to be conveniently and reliably assessed
with other approaches. Moreover, we show that SPR-recognized fibril fragments are more toxic than
the larger fibrillar structures, suggesting the relevance of the proposed SPR-based immunoassay