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Summary
In?vitro, ¦Â-amyloi
d (A¦Â) pepti
des form polymorphic fibrils, with molecular structures that
depen
d on growth con
ditions, plus various oligomeric an
d protofibrillar aggregates. Here, we investigate structures of human brain-
derive
d A¦Â fibrils, using see
de
d fibril growth from brain extract an
d data from soli
d-state nuclear magnetic resonance an
d electron microscopy. Experiments on tissue from two Alzheimer¡¯s
disease (AD) patients with
distinct clinical histories showe
d a single pre
dominant 40 resi
due A¦Â (A¦Â40) fibril structure in each patient; however, the structures were
different from one another. A molecular structural mo
del
develope
d for A¦Â40 fibrils from one patient reveals features that
distinguish in-vivo- from in-vitro-pro
duce
d fibrils. The
data suggest that fibrils in the brain may sprea
d from a single nucleation site, that structural variations may correlate with variations in AD, an
d that structure-specific amyloi
d imaging agents may be an important future goal.
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