Page 373 - Organic Electronics in Sensors and Biotechnology

350 Chapter Nine

pH (pH 2). All the LCPs stained amyloid plaques associated with sys-
temic amyloidoses and local amyloidoses, such as type 2 diabetes
and Alzheimer’s disease (AD). Similar to results obtained on in vitro
formed amyloid fibrils, PTAA shows a red-shifted spectrum with a
maximum around 580 nm upon binding to amyloid plaques, whereas
amyloid deposits stained by PONT emit light with a more green-
yellowish hue. Hence, upon binding to amyloid plaques in tissue
samples, the rotational freedom of the thiophene rings and the geom-
etry of the backbone are restricted, leading to a specific emission pro-
file from the LCP similar to what was observed on pure amyloid
fibrils in solution. Furthermore, some results were suggesting that
PTAA emits light of different colors upon binding to different amyloid
subtypes. 110
The conformation-induced change of the fluorescence is a unique
property seen for LCPs that cannot be achieved by sterically rigid
conventional amyloid ligands dyes such as thioflavin T (ThT) and
Congo red. Thus, LCPs offer the possibility to obtain a specific spec-
troscopic signature for individual protein aggregates. As mentioned
earlier, there are many fundamental questions regarding this aggrega-
tion process that remain unanswered, and the underlying mechanism
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of amyloid or protein aggregate formation is poorly understood. In
this regard, the technique using LCPs, which provides a direct link
between spectral signal and protein conformation, might provide an
opportunity to gain more information concerning the morphology of
the protein deposits and might facilitate a greater understanding of
the conformational phenotype encoded in the protein aggregates.
Instead of looking at the total amount of protein aggregates, hetero-
genic population of specific protein aggregates could be observed,
and novel findings regarding toxic species and the molecular mecha-
nism of these diseases could be obtained with the LCP technique.
These assumptions have also been verified with experimental data
using transgenic mouse model having AD pathology and transgenic
mice infected with distinct prion strains. 111–112
Upon application of LCPs to transgenic mouse models having
AD pathology, a striking heterogenicity in the characteristic plaques
composed of the A-beta peptide was identified. LCP staining of
111
brain tissue slices revealed different subpopulations of plaques, seen
as plaques with different colors (Fig. 9.9). The spectral features of
LCPs enable an indirect mapping of the plaque architecture, as the
different colors of the LCPs are associated with different conforma-
tions of the polymer backbone. These findings can lead to novel ways
of diagnosing AD and also provide a new method for studying the
pathology of the disease in a more refined manner. Especially, the
LCP technique might be valuable for identifying distinct toxic entities
giving rise to cell death and loss of neurons, or for establishing a cor-
relation between the type of plaque and the severity of AD. However,