RT Conference Proceedings
T1 Amyloid-b seeding and propagation processes in a hAb-KI model of Alzheimer's disease
A1 Trujillo-Estrada, Laura Isabel
A1 Do Huynh, Kelly
A1 Minh Thu Nguyen, Marie
A1 Cheung, Alwin
A1 Pham Tran, Janine
A1 Núñez-Díaz, Cristina
A1 Forner, Stefania
A1 Martini, Alessandra C.
A1 Da Cunha, Celia
A1 Shahnawaz, Mohammad
A1 Soto, Claudio
A1 Moreno-González, Inés
A1 Gutiérrez-Pérez, Antonia
A1 LaFerla, Frank
A1 Baglietto-Vargas, David
K1 Alzheimer, enfermedad de
AB Recent evidence indicates that Aβ can misfold and aggregate into seeds thatstructurally corrupt native proteins, mimicking a prion-like process. Severalstudies using FAD animal models have demonstrated that intracerebralinfusion of brain extracts from APP-transgenic mice or AD patients induceAβ deposition and cerebral amyloid angiopathy. To carry out most of theseAβ-seeding studies, APP-transgenic animal have been used. Nevertheless, itremains to be elucidated whether Aβ deposition can be induced by Aβ-seedsin a sporadic AD model that does not overexpress APP and produces wildtype human Aβ.We used an innovative model to better understand the amyloidogenic eventsthat occur in sporadic AD. This hAβ-KI model, expresses wild-type humanAβ under the control of the endogenous mouse APP gene. Aβ-seeds fromAD patients (stage C) from the AD Research Center (UCI) wereadministered into 7-8-month-old hAβ-KI and as positive controls 3xTg-ADmice were employed.We demonstrated that amyloid seeds can stimulate Aβ aggregations in3xTg-AD and hAβ-KI models. We found that Aβ aggregates occur earlierin the 3xTg-AD vs hAβ-KI and that a longer term of treatment is necessaryto accelerate diffusible Aβ pathology in the hAβ-KI mice. Thereferoe, thishAβ-KI model represents an important step towards the development ofnext-generation animal models that will provide better predictive outcomesfor human patients.Grants support: UCI MIND Pilot project (DBV), Ministry of SciencePID2019-108911RA-100 (DBV), U54 AG054349 (FML), Institute ofHealth Carlos III PI18/01557 (AG) co-financed by FEDER funds (EuropeanUnion), NIH/NIA Grant P50 AG16573 (UCI-ADRC).
YR 2020
FD 2020-12-17
LK https://hdl.handle.net/10630/20634
UL https://hdl.handle.net/10630/20634
LA eng
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026