Prion-like transmission and propagation of human β-amyloid to the bank vole rodent model

Over the past decades, growing experimental and observational evidence has suggested that Aβ and pTau, the hallmarks of Alzheimer's disease (AD), may spread through the nervous system via a prion-like mechanism. Here, we investigated the transmissibility of Aβ and pTau by inoculating bank voles, a wild-type rodent highly susceptible to prion diseases, with brain homogenates from four sporadic and five familial AD-affected patients. We observed that (i) neo-formed Aβ deposits and pTau inclusions were induced in recipient vole brains; (ii) Aβ pathology appeared to follow a specific neurotropic distribution; (iii) Aβ proteinopathy propagated through vole-to-vole inoculation. Our findings provide the first experimental evidence that human Aβ seeds are transmissible to a wild-type rodent model, further supporting the prion-like nature of Aβ. These results strongly support recent studies suggesting iatrogenic Aβ transmission, underscoring the need to evaluate the impact of Aβ seed exposure on human health.

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Publication Details

Journal
Acta Neuropathologica
Published
2026-06-30
DOI
https://doi.org/10.1007/s00401-026-03041-2
Primary Topic
Prion Diseases and Protein Misfolding
Type
article
Field-Weighted Citation Impact
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article

Prion-like transmission and propagation of human β-amyloid to the bank vole rodent model

Giuseppe Legname, Umberto Agrimi, Geraldina Riccardi, Giorgio Giaccone et al.
Acta Neuropathologica
Prion Diseases and Protein Misfolding
article

Prion-like transmission and propagation of human β-amyloid to the bank vole rodent model

Giuseppe Legname, Umberto Agrimi, Geraldina Riccardi, Giorgio Giaccone, Michele Angelo Di Bari, C D'Agostino, Marcella Catania, Fabio Moda, Franco Cardone, Rosalia Bruno, Giuseppe Di Fede, Anna Burato, Elena De Cecco, Ilaria Vanni, Romolo Nonno, Fabrizio Tagliavini
article en

Abstract

Over the past decades, growing experimental and observational evidence has suggested that Aβ and pTau, the hallmarks of Alzheimer's disease (AD), may spread through the nervous system via a prion-like mechanism. Here, we investigated the transmissibility of Aβ and pTau by inoculating bank voles, a wild-type rodent highly susceptible to prion diseases, with brain homogenates from four sporadic and five familial AD-affected patients. We observed that (i) neo-formed Aβ deposits and pTau inclusions were induced in recipient vole brains; (ii) Aβ pathology appeared to follow a specific neurotropic distribution; (iii) Aβ proteinopathy propagated through vole-to-vole inoculation. Our findings provide the first experimental evidence that human Aβ seeds are transmissible to a wild-type rodent model, further supporting the prion-like nature of Aβ. These results strongly support recent studies suggesting iatrogenic Aβ transmission, underscoring the need to evaluate the impact of Aβ seed exposure on human health.

Acta NeuropathologicaVol. 151(1)
Scuola Internazionale Superiore di Studi Avanzati (IT), University of Milan (IT), University of Zurich (CH), Istituto Superiore di Sanità (IT), Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
Openalex Percentile: Top 12%
Prion Diseases and Protein Misfolding
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