RT Journal Article
T1 Two structurally defined Aβ polymorphs promote different pathological changes in susceptible mice.
A1 Gómez Gutiérrez, Rubén
A1 Ghosh, Ujjayini
A1 Yau, Wai‐Ming
A1 Gámez, Nazaret
A1 Do, Katherine
A1 Kramm, Carlos
A1 Shirani, Hamid
A1 Vegas-Gómez, Laura
A1 Schulz, Jonathan
A1 Moreno-González, Inés
A1 Gutiérrez-Pérez, Antonia
A1 Nilsson, K. Peter R.
A1 Tycko, Robert
A1 Soto, Claudio
A1 Morales, Rodrigo
K1 Amiloide
K1 Proteínas - Estructura
K1 Priones
K1 Modelos animales en investigación
AB Misfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain‐specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, tropism to specific brain regions, differential recruitment of Aβ40/Aβ42 peptides, and induction of microglial and astroglial responses. Importantly, the aggregates induced by 2F and 3F are structurally different as determined by ssNMR. Our study analyzes the biological properties of purified Aβ polymorphs that have been characterized at the atomic resolution level and provides relevant information on the pathological significance of misfolded Aβ strains
PB EMBO Press
YR 2023
FD 2023-08-03
LK https://hdl.handle.net/10630/39656
UL https://hdl.handle.net/10630/39656
LA eng
NO Gomez-Gutierrez R, Ghosh U, Yau WM, Gamez N, Do K, Kramm C, Shirani H, Vegas-Gomez L, Schulz J, Moreno-Gonzalez I, Gutierrez A, Nilsson PR, Tycko R, Soto C, Morales R. Two structurally defined Aβ polymorphs promote different pathological changes in susceptible mice. EMBO Reports (2023). e57003 10.15252/embr.202357003
NO © 2023 The Authors
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 4 mar 2026