The aggregation and malformation of the Amyloid beta peptide abeta(1-40) is
strongly believed to be involved in the development of Alzheimer's disease
(AD). With this thesis we hope to provide important clues to further
understanding of amyloid formation in vitro, near physiological conditions.
We use the Atomic Force Microscope (AFM) which provides three-dimensional
images with vertical resolution down to Angstroms. Together with a
previously developed add on tapping mode system we investigate the
aggregation paths for abeta(1-40) in three different relevant physiological
buffer solutions. The AFM system is extended with an external data
acquisition system for increased image resolution. Our results show that
protein aggregation can be very complex, many different intermediates with a
large variety of morphologies are observed, including protofibrils and large
mature fibrils. Our results also indicate that the appearance of
protofibrils, i.e. an intermediate stage in the fibrillization, depends on
the peptide concentration. It is also shown that pretreatment of samples are
very important, there are large differences in aggregation behaviour
between a freshly prepared abeta(1-40) sample and a sample that has been
frozen prior to experiments, due to a degradation of peptide concentration.
The addition of sodium chloride to the sample reveals an increased
aggregation process, fibrils were seen two days earlier than for
abeta(1-40). Also shown is that too large amounts of such [Cl] ions in the
buffer solution rearranges the fibrils structure into amorphous aggregates.
Aluminium has for many years been suggested as a possible cause in the
development of AD. The addition of an aluminium citrate, stable at relevant
pH, shows that the aggregation process towards fibrillization is increased,
and these fibrils show no tendency of instability. The mature fibrils in the
case of added aluminium citrate have ...
