2026-05-27T05:30:33Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/396562026-02-03T11:11:31Zcom_10630_2254col_10630_37953

00925njm 22002777a 4500 dc Gómez Gutiérrez, Rubén author Ghosh, Ujjayini author Yau, Wai‐Ming author Gámez, Nazaret author Do, Katherine author Kramm, Carlos author Shirani, Hamid author Vegas-Gómez, Laura author Schulz, Jonathan author Moreno-González, Inés author Gutiérrez-Pérez, Antonia author Nilsson, K. Peter R. author Tycko, Robert author Soto, Claudio author Morales, Rodrigo author 2023-08-03 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 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 https://hdl.handle.net/10630/39656 10.15252/embr.202357003 Amiloide Proteínas - Estructura Priones Modelos animales en investigación Two structurally defined Aβ polymorphs promote different pathological changes in susceptible mice.