Altering Brain Amyloidosis by Intra-Lingual and Extra-Nasal Exposure of Aβ Aggregates

Authors

Nazaret Gamez
Javiera Bravo-Alegria
Yumeng Huang
Nelson Perez-Urrutia
Deepa Dongarwar
Claudio Soto
Rodrigo Morales

Publication Date

10-31-2022

Journal

Cells

Abstract

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.

Keywords

Animals, Mice, Humans, Amyloid beta-Peptides, Alzheimer Disease, Mice, Transgenic, Brain, Amyloidosis, Tongue

Comments

Supplementary Materials

Data Availability Statement

PMID: 36359840