RT Conference Proceedings
T1 Human and mouse Alzheimer’s seeds differentially affect amyloid and tau aggregates in aged mice
A1 Andreo-López, Juana
A1 Bettinetti-Luque, Miriam
A1 Campos-Moreno, Cynthia
A1 García-León, Juan Antonio
A1 Morales-Cabello, Mario
A1 Núñez-Diaz, Cristina
A1 Zimbone, Stefania
A1 Bellia, Francesco
A1 Giuffrida, Maria Laura
A1 Cadete Martini, Alessandra
A1 Forner, Stefania
A1 Gamez, Nazaret
A1 Morales, Rodrigo
A1 Gutiérrez-Pérez, Antonia
A1 LaFerla, Frank
A1 Baglietto-Vargas, David
A1 Baglietto-Vargas, David
K1 Alzheimer, Enfermedad de
AB Alzheimer's disease (AD) is a complex neurodegenerative proteinopathy in which Aβ and tau misfold and aggregate into entities that structurally unsettle native proteins, mimicking a prion-like or “seeding” process. These Aβ and tau “seeds” can arrange in different conformations or strains that might display distinct pathogenic properties. Furthermore, recent evidence suggest that microglia play a key role in the amyloidogenic event and can modulate the propagation and aggregation processes. Here, we investigated whether amyloid seeds from human AD brains compared to those from transgenic mice (3xTg-AD) are more prone to induce Aβ and tau aggregates in vivo, as well as potential differences in the microglial response to the plaque pathology. We employed histological and molecular approaches to determine the Aβ/tau pathology and Aβ-seeding capacity of brain extracts derived from postmortem AD cortex versus aged 3xTg-AD mice (25-month-old). Brain homogenates were injected into the hippocampus of 3xTg-AD mice and examined at 17-18 months of age. The seeds from the human AD brain induced more aggressive amyloid pathology compared to seeds from aged 3xTg-AD mice. However, the AD seeds from aged transgenic mice triggered more tau pathology. Interestingly, such mice seeds impaired microglial clustering around plaques leading to more severe neuritic pathology. These results suggest that multiple variables such as the AD seed, recipient model and time, are critical factors that can modulate the amyloid pathology onset and progression. Thus, more profound understanding on these factors will provide key insight on how amyloid pathology progresses in AD.
YR 2025
FD 2025-09-03
LK https://hdl.handle.net/10630/45273
UL https://hdl.handle.net/10630/45273
LA eng
NO 'PID2019-108911RA-100
NO PID2024-161545OB-100
NO AARG-22-928219
NO U54-AG054349
NO R01AI132695
NO AARGD-22-972125
NO U42OD11158
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 12 abr 2026