  Experimental evidence suggests that the folding and aggregation of the
amyloid $\beta$-protein (A$\beta$) into oligomers is a key pathogenetic event
in Alzheimer's disease (AD). Inhibiting the pathologic folding and
oligomerization of A$\beta$ could be effective in the prevention and treatment
of AD. Here, using all-atom molecular dynamics simulations in explicit solvent,
we probe the initial stages of folding of a decapeptide segment of A$\beta$,
A$\beta_{21-30}$, shown experimentally to nucleate the folding process. In
addition, we examine the folding of a homologous decapeptide containing an
amino acid substitution linked to hereditary cerebral hemorrhage with
amyloidosis--Dutch type, [Gln22]A$\beta_{21-30}$. We find that: (i) when the
decapeptide is in water, hydrophobic interactions and transient salt bridges
between Lys28 and either Glu22 or Asp23 are important in the formation of a
loop in the Val24--Lys28 region of the wild type decapeptide; (ii) in the
presence of salt ions, salt bridges play a more prominent role in the
stabilization of the loop; (iii) in water with a reduced density, the
decapeptide forms a helix, indicating the sensitivity of folding to different
aqueous environments; (iv) the ``Dutch'' peptide in water, in contrast to the
wild type peptide, fails to form a long-lived Val24--Lys28 loop, suggesting
that loop stability is a critical factor in determining whether A$\beta$ folds
into pathologic structures. Our results are relevant to understand the
mechanism of A$\beta$ peptide folding in different environments, such as intra-
and extracellular milieus or cell membranes, and how amino acid substitutions
linked to familial forms of amyloidosis cause disease.
