2026-05-31T06:20:57Zhttps://riuma.uma.es/rest/oai/requestoai:riuma.uma.es:10630/180892026-02-03T12:20:56Zcom_10630_2254col_10630_37959
RIUMA. Repositorio Institucional de la Universidad de Málaga
author
Sánchez-Varo, Raquel María
author
Fernández-Valenzuela, Juan José
author
Romero-Molina, Carmen
author
Sánchez-Mejías, Elisabeth
author
Gómez-Arboledas, Ángela
author
Núñez-Díaz, Cristina
author
Navarro, Victoria
author
Dávila-Cansino, José Carlos
author
Vitorica Ferrández, Javier
author
Gutiérrez-Pérez, Antonia
2019-07-19T07:53:37Z
2019-07-19T07:53:37Z
2019-07-19
https://hdl.handle.net/10630/18089
Amyloid-beta (Abeta) peptide deposits and hyperphosphorylated tau protein (phospho-tau) accumulate in
Alzheimer’s disease (AD) brains. These abnormal protein aggregates leads to glial activation, synaptic
dysfunction, neuronal loss and cognitive decline. While microglial response has mostly been analyzed in relation to Abeta accumulation, little is still known about inflammatory processes associated with tau pathology. Microglial reactivity and defective glial responses have been involved in these proteinopathies. Our aim is to clarify the effects of Abeta and tau separately, in order to improve the comprehension of their differential contribution to neuroinflammation and neurodegeneration. We compared the progression of these processes in an amyloidogenic AD model (APPSL/PS1M146L) and two different models of tauopathy (ThyTau22 and hP301S) from 2 to 18 months of age. Accumulation of aggregated proteins was assessed using specific anti- Abeta and phospho-tau antibodies. Inflammatory response was studied using a battery of microglial markers (Iba1, CD45, CD68, Trem2 and Gal-3). In the hippocampus of these models, Tau and Abeta pathologies initiated as early as 2 months of age and increased progressively with aging. Neuritic plaques induced a strong microglial activation associated to plaques in APP/PS1 mice. Interestingly, inflammatory markers and microglial reactivity were barely increased in the hippocampus of ThyTau mice in contrast to not only APP/PS1, but also to P301S mice, which displayed a prominent microglial response. Deciphering the specific effects of Abeta, tau and their different toxic species, would indeed enable the development of novel therapeutic strategies and drugs targeting neuroinflammatory pathways related to these proteinopathies.
eng
Células gliales
Bilología celular
Genética
Fisiología
Dissecting the microglial response in transgenic models of amyloidogenesis and tauopathy
conference output
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URL
https://riuma.uma.es/bitstreams/f747be48-354b-4823-88d1-b92c8b14e9d9/download
File
MD5
0b1f858cea62fd3189a95e5955ee6c6f
161674
application/pdf
Sanchez-Varo.pdf