Alzheimer’s disease is linked to amyloid β (Aβ) peptide aggregation in the brain, and a
detailed understanding of the molecular mechanism of Aβ aggregation may lead to improved
diagnostics and therapeutics. While previous studies have been performed in pure buffer, we
approach the mechanism in vivo using cerebrospinal fluid (CSF). We investigated the
aggregation mechanism of Aβ42 in human CSF through kinetic experiments at several Aβ42
monomer concentrations (0.8–10 µM). The data were subjected to global kinetic analysis and
found consistent with an aggregation mechanism involving secondary nucleation of monomers on the fibril surface. A mechanism only including primary nucleation was ruled out. We
find that the aggregation process is composed of the same microscopic steps in CSF as in
pure buffer, but the rate constant of secondary nucleation is decreased. Most importantly, the
autocatalytic amplification of aggregate number through catalysis on the fibril surface is
prevalent also in CSF
