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polymerizes into fibrils in a nucleation dependent
reaction, involving several intermediate species, some of them being
neurotoxic. Inhibitors that block the formation of such toxic intermedi-
ates may be used for the treatment of Alzheimer's disease. A central
region of A
Monomeric A
β
β
is crucial for A
β
-A
β
interactions, and compounds binding
to this region can inhibit A
-polymerization. Such compounds have
shown beneficial effects in transgenic mice and a couple of them have
been tested in clinical trials, but the results are so far not convincing.
Several different techniques have been used to study A
β
-polymerization.
They all have their merits and drawbacks, and no single technique can
give the full picture on its own. Hopefully, technical and methodological
development will provide a more detailed understanding of the polymer-
ization process and aid in the search for more efficient inhibitors that are
therapeutically useful.
β
Acknowledgment
This work was supported by Stiftelsen Demensfonden, Stockholm,
Sweden.
References
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antiparallel, organization of beta-sheets in Alzheimer's
β
-amyloid
fibrils.
Proc Nat Acad Sci USA
97
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-amyloid fibrils from electron
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41
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β
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