Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models

Author:

de la Cueva Macarena,Antequera Desiree,Ordoñez-Gutierrez Lara,Wandosell Francisco,Camins Antonio,Carro EvaORCID,Bartolome FernandoORCID

Abstract

AbstractThe most accepted hypothesis in Alzheimer’s disease (AD) is the amyloid cascade which establishes that Aβ accumulation may induce the disease development. This accumulation may occur years before the clinical symptoms but it has not been elucidated if this accumulation is the cause or the consequence of AD. It is however, clear that Aβ accumulation exerts toxic effects in the cerebral cells. It is important then to investigate all possible associated events that may help to design new therapeutic strategies to defeat or ameliorate the symptoms in AD. Alterations in the mitochondrial physiology have been found in AD but it is not still clear if they could be an early event in the disease progression associated to amyloidosis or other conditions. Using APP/PS1 mice, our results support published evidence and show imbalances in the mitochondrial dynamics in the cerebral cortex and hippocampus of these mice representing very early events in the disease progression. We demonstrate in cellular models that these imbalances are consequence of Aβ accumulation that ultimately induce increased mitophagy, a mechanism which selectively removes damaged mitochondria by autophagy. Along with increased mitophagy, we also found that Aβ independently increases autophagy in APP/PS1 mice. Therefore, mitochondrial dysfunction could be an early feature in AD, associated with amyloid overload.

Funder

Instituto de Salud Carlos III

Dirección General de Universidades e Investigación

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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