Amyloid, The Amyloid B -Peptide and Alzheimer’s Disease: Structural Considerations - Molecules: Nucleation, Aggregation and Crystallization - page 297

in the simultaneous detection of red and green light when they pass the
volume element.

Inhibition of A β Polymerization

The polymerization of A leads to the formation of toxic species, and

thus, interfering with this process is a potential strategy for the prevention
and treatment of AD. Since oligomeric A

β

species are toxic, the inhibitors
should stop the polymerization process as early as possible. As described
above, it is difficult to study A

β

-polymerization, and finding polymeriza-
tion inhibitors is therefore a complicated task. Moreover, the inhibitors
should be stable, non-toxic, and pass the blood-brain barrier. Usually, a
drug that acts as an inhibitor is directed to a well-defined site, e.g. the
active site of a protein with a defined structure. Since monomeric A

β

is in
a mostly random conformation, no such site exists, but there could still be
regions in A

β

interactions.
In order to investigate whether a specific region in A

β that are highly important for A β -A β

β could be cru-

cial for A β -polymerization, peptide sequences corresponding to A β 1-10,

A 31-40, were synthesized on a membrane. The

membrane, containing 31 spots with different peptides, was then incu-
bated with radiolabeled A

β 2-11, A β 3-12, …, A β

1-40 was
detected by exposing an X-ray sensitive film to the membrane. It was
found that peptides corresponding to the central region of A

β 1-40. After washing, bound A β

mediated the
strongest binding. By synthesizing a variety of shorter peptides, it was
shown that A

β

16-20 (LysLeuValPhePhe or KLVFF in one letter code)
was sufficient for mediating A

β

binding (Tjernberg et al ., 1996). A
peptide containing this sequence was synthesized and incubated together
with A

β -A β

1-40. Only a few fibrils were observed by EM in this sample
while a massive network of fibril bundles were found after incubation of
A

β

1-40 in the absence of the short peptide. Hence, a short peptide that
binds to the KLVFF region in A

β

can inhibit fibril formation. Such a pep-
tide is not useful for the treatment of AD, since it is rapidly degraded in
the human body, but modifications making it more stable towards prote-
olytic degradation are possible. For instance, peptides composed of

β