This study addressed two main aims relating to the Aβ1-42 peptide – widely demonstrated to
play a key role in the pathogenesis of Alzheimer’s Disease (AD). Aβ1-42 is an amyloid peptide
that readily self-associates forming neurotoxic aggregates. With the primary risk factor for
AD being age, and ageing populations increasing, the need for research into methods of
reducing the levels of Aβ1-42 aggregates has never been greater. The first aim of this study
was to recombinantly produce the Aβ1-42 peptide using a previously published protocol in
order to produce stocks for future experimental use. Producing Aβ1-42 recombinantly results
in less peptide variability than occurs via peptide synthesis, and is a much cheaper source of
the peptide than commercial procurement. The peptide was expressed by induction of
Escherichia coli to express a fusion protein encoding the Aβ1-42 peptide in addition to specific
regions necessary for purification. Analysis of the purified Aβ1-42 peptide by transmission
electron microscopy demonstrated that the peptide was able to self-associate forming a
variety of structures characteristic of Aβ1-42 aggregation as illustrated in the literature. The
second aim of the study was to evalauate the effect of Peptide Inhibitor NanoParticles
(PINPs) upon Aβ1-42 aggregation. PINPs are second-generation liposomes with the RI-OR2-
TAT peptide attached to the surface. RI-OR2-TAT has been found previously to reduce Aβ1-42
aggregation in mouse models of AD. Analysis of the effect of PINPs upon Aβ1-42 aggregation
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was performed using transmission electron microscopy and fluorescence based assays with
PINPs being found to directly bind early and late stage Aβ1-42 aggregates and reduce levels of
aggregation. Based on the findings of this study, amendments to the Aβ1-42 production
protocol are proposed and it is recommended that PINPs be carried forward into clinical
trials as a potential treatment option for AD.