PMCA-generated prions from the olfactory mucosa of patients with Fatal Familial Insomnia cause prion disease in mice.

ABSTRACT:

Background

Fatal Familial Insomnia (FFI) is a genetic prion disease caused by the D178N mutation in the prion protein gene (PRNP) in coupling phase with methionine at PRNP 129. In 2017, we have shown that the olfactory mucosa (OM) collected from FFI patients contained traces of PrPSc detectable by Protein Misfolding Cyclic Amplification (PMCA).

Methods

In this work, we have challenged PMCA-generated products obtained from OM and brain homogenate of FFI patients in BvPrP-Tg407 transgenic mice expressing the bank vole prion protein to test their ability to induce prion pathology.

Results

All inoculated mice developed mild spongiform changes, astroglial activation, and PrPSc deposition mainly affecting the thalamus. However, their neuropathological alterations were diffe

SUBMITTER: Bistaffa E 

PROVIDER: S-EPMC8064759 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature