Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease.

ABSTRACT: Mitochondria contribute to shape intraneuronal Ca²⁺ signals. Excessive Ca²⁺ taken up by mitochondria could lead to cell death. Amyloid beta (Aβ) causes cytosolic Ca²⁺ overload, but the effects of Aβ on mitochondrial Ca²⁺ levels in Alzheimer's disease (AD) remain unclear. Using a ratiometric Ca²⁺ indicator targeted to neuronal mitochondria and intravital multiphoton microscopy, we find increased mitochondrial Ca²⁺ levels associated with plaque deposition and neuronal death in a transgenic mouse model of cerebral β-amyloidosis. Naturally secreted soluble Aβ applied onto the healthy brain increases Ca²⁺ concentration in mitochondria, which is prevented by blockage of the mitochondrial calcium uniporter. RNA-sequencin

SUBMITTER: Calvo-Rodriguez M 

PROVIDER: S-EPMC7195480 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature