Title:Amyloid-β in the Cerebrospinal Fluid of APP Transgenic Mice Does not Show Prion-like Properties
Volume: 12
Issue: 9
Author(s): Zhiva Skachokova, Frederik Sprenger, Karin Breu, Dorothee Abramowski, Florence Clavaguera, Jurgen Hench, Matthias Staufenbiel, Markus Tolnay and David T. Winkler
Affiliation:
Keywords:
Alzheimer's disease, amyloid-beta, Aβ, prion, cerebrospinal fluid, diagnostics, transgenic mouse models.
Abstract: Early diagnosis of Alzheimer`s disease (AD) is currently difficult and involves a complex approach including
clinical assessment, neuroimaging, and measurement of amyloid-β (Aβ) and tau levels in cerebrospinal fluid (CSF). A better
mechanistic understanding is needed to develop more accurate and even presymptomatic diagnostic tools. It has been
shown that Aβ derived from amyloid-containing brain tissue has prion-like properties: it induces misfolding and aggregation
of Aβ when injected into human amyloid precursor protein (APP) transgenic mice. In contrast, Aβ in the CSF has
been less studied, and it is not clear whether it also exhibits prion-like characteristics, which might provide a sensitive diagnostic
tool. Therefore, we collected CSF from APP transgenic mice carrying the Swedish mutation (APP23 mice), and
injected it intracerebrally into young mice from the same transgenic line. We found that CSF derived Aβ did not induce
increased β-amyloidosis, even after long incubation periods and additional concentration. This suggests that Aβ present in
the CSF does not have the same prion-like properties as the Aβ species in the brain.
