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

Extensive experimental and human-derived evidence suggest that misfolded A beta particles spread similarly to infectious prions. Moreover, peripheral administration of A beta seeds accelerates brain amyloidosis in both susceptible experimental animals and humans. The mechanisms and elements governing the transport of misfolded A beta 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 A beta seeds in the tongue, a highly innervated organ, substantially accelerates the appearance of plaques in Tg2576 mice. In addition, the extra-nasal exposure of A beta aggregates increased amyloid pathology in the olfactory bulb. Our results show that exposing highly innervated tissues to A beta seeds accelerates AD-like pathological features, and suggest that A beta 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 A beta misfolding.