Templated seeding induces the formation of Alzheimer paired helical tau filaments in human brain organoids
- 1University of Cambridge
Abstract
The prion concept postulates that seeded aggregation results in the recruitment of soluble protein monomers and their assembly into amyloid filaments with the same structures as those of the seeds. Here we show that this concept applies to tau filaments formed in cortical organoids obtained from human iPSCs of control subjects. Tau seeds were extracted from the frontal cortex of individuals with Alzheimer disease. When added to human cortical organoids expressing endogenous levels of three-repeat tau, they gave rise to filaments of three-repeat tau whose formation required endogenous tau expression. By cryo-EM, these seeded tau filaments were identical to the paired helical filaments of the seeds. This novel finding demonstrates the faithful templated seeding of tau in human nerve cells expressing endogenous levels of tau and opens the way to studying the mechanisms of paired helical filament formation and their downstream effects in a human system amenable to genetic modification.
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BibTeX
@misc{bacioglu2026templated,
title = {{Templated seeding induces the formation of Alzheimer paired helical tau filaments in human brain organoids}},
author = {M. Bacioglu and T. Katsinelos and M. Schweighauser and F. Gallo and K. Mueller and R. Christou and J. Brandes and S. Lovestam and S. A. Cowley and W. A. McEwan and S. Scheres and M. Goedert and M. G. Spillantini},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.755295},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755295v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Templated seeding induces the formation of Alzheimer paired helical tau filaments in human brain organoids
AU - M. Bacioglu
AU - T. Katsinelos
AU - M. Schweighauser
AU - F. Gallo
AU - K. Mueller
AU - R. Christou
AU - J. Brandes
AU - S. Lovestam
AU - S. A. Cowley
AU - W. A. McEwan
AU - S. Scheres
AU - M. Goedert
AU - M. G. Spillantini
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.755295
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.755295v1
AB - The prion concept postulates that seeded aggregation results in the recruitment of soluble protein monomers and their assembly into amyloid filaments with the same structures as those of the seeds. Here we show that this concept applies to tau filaments formed in cortical organoids obtained from human iPSCs of control subjects. Tau seeds were extracted from the frontal cortex of individuals with Alzheimer disease. When added to human cortical organoids expressing endogenous levels of three-repeat tau, they gave rise to filaments of three-repeat tau whose formation required endogenous tau expression. By cryo-EM, these seeded tau filaments were identical to the paired helical filaments of the seeds. This novel finding demonstrates the faithful templated seeding of tau in human nerve cells expressing endogenous levels of tau and opens the way to studying the mechanisms of paired helical filament formation and their downstream effects in a human system amenable to genetic modification.
ER -