Amyloid-ß in the Cerebrospinal Fluid of APP Transgenic Mice Does not Show Prion-like Properties.

ABSTRACT

Early diagnosis of Alzheimer`s disease (AD) is currently difficult and involves a complex approach including clinical assessment, neuroimaging, and measurement of amyloid-ß (Aß) 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 Aß derived from amyloid-containing brain tissue has prion-like properties it induces misfolding and aggregation of Aß when injected into human amyloid precursor protein (APP) transgenic mice. In contrast, Aß 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 Aß did not induce increased ß-amyloidosis, even after long incubation periods and additional concentration. This suggests that Aß present in the CSF does not have the same prion-like properties as the Aß species in the brain.