RT Journal Article
T1 Altering Brain Amyloidosis by Intra-Lingual and Extra-Nasal Exposure of Aβ Aggregates.
A1 Gamez, Nazaret
A1 Bravo-Alegria, Javiera
A1 Huang, Yumeng
A1 Perez-Urrutia, Nelson
A1 Dongarwar, Deepa
A1 Soto, Claudio
A1 Morales, Rodrigo
K1 Alzheimer’s disease
K1 amyloid-beta
K1 nasal cavity
K1 prion
K1 tongue
AB Extensive experimental and human-derived evidence suggest that misfolded Aβ particles spread similarly to infectious prions. Moreover, peripheral administration of Aβ seeds accelerates brain amyloidosis in both susceptible experimental animals and humans. The mechanisms and elements governing the transport of misfolded Aβ from the periphery to the brain are not fully understood, although circulation and retrograde axonal transport have been proposed. Here, we demonstrate that injection of Aβ seeds in the tongue, a highly innervated organ, substantially accelerates the appearance of plaques in Tg2576 mice. In addition, the extra-nasal exposure of Aβ aggregates increased amyloid pathology in the olfactory bulb. Our results show that exposing highly innervated tissues to Aβ seeds accelerates AD-like pathological features, and suggest that Aβ seeds can be transported from peripheral compartments to the brain by retrograde axonal transport. Research in this direction may be relevant on different fronts, including disease mechanisms, diagnosis, and risk-evaluation of potential iatrogenic transmission of Aβ misfolding.
YR 2022
FD 2022-10-31
LK http://hdl.handle.net/10668/20938
UL http://hdl.handle.net/10668/20938
LA en
DS RISalud
RD Apr 6, 2025