RT Journal Article
T1 Intra- and extracellular β-amyloid overexpression via adeno-associated virus-mediated gene transfer impairs memory and synaptic plasticity in the hippocampus
A1 Forner, Stefania
A1 Martini, Alessandra
A1 Prieto, Gilberto Aleph
A1 Dang, Cindy
A1 Rodriguez-Ortiz, Carlos
A1 Reyes Ruiz, Jorge Mauricio
A1 Trujillo-Estrada, Laura Isabel
A1 da Cunha, Celia
A1 Andrews, Elizabeth
A1 Phan, Jimmy
A1 Ha, Jordan
A1 Chang, Allissa
A1 Levites, Yona
A1 Cruz, Pedro
A1 Ager, Rahasson
A1 Medeiros, Rodrigo
A1 Kitazawa, Masashi
A1 Glabe, Charles
A1 Cotman, Carl
A1 Golde, Todd
A1 Baglietto-Vargas, David
A1 LaFerla, Frank M
A1 Baglietto-Vargas, David
K1 Alzheimer, Enfermedad de
AB Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is currently conceptualized as a disease of synaptic failure. Synaptic impairments are robust within the AD brain and better correlate with dementia severity when compared with other pathological features of the disease. Nevertheless, the series of events that promote synaptic failure still remain under debate, as potential triggers such as β-amyloid (Aβ) can vary in size, configuration and cellular location, challenging data interpretation in causation studies. Here we present data obtained using adeno-associated viral (AAV) constructs that drive the expression of oligomeric Aβ either intra or extracellularly. We observed that expression of Aβ in both cellular compartments affect learning and memory, reduce the number of synapses and the expression of synaptic-related proteins, and disrupt chemical long-term potentiation (cLTP). Together, these findings indicate that during the progression AD the early accumulation of Aβ inside neurons is sufficient to promote morphological and functional cellular toxicity, a phenomenon that can be exacerbated by the buildup of Aβ in the brain parenchyma. Moreover, our AAV constructs represent a valuable tool in the investigation of the pathological properties of Aβ oligomers both in vivo and in vitro.
PB Springer Nature
YR 2019
FD 2019-11
LK https://hdl.handle.net/10630/34439
UL https://hdl.handle.net/10630/34439
LA spa
NO Forner, S., Martini, A.C., Prieto, G.A. et al. Intra- and extracellular β-amyloid overexpression via adeno-associated virus-mediated gene transfer impairs memory and synaptic plasticity in the hippocampus. Sci Rep 9, 15936 (2019). https://doi.org/10.1038/s41598-019-52324-0
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 12 abr 2026