Schaefer 2016 Abstract ADFLIM 2016

From Bioblast
ADFLIM in AD research โ€“imaging mitochondrial function in Alzheimerยดs disease

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Patrick Schaefer

Schaefer PM, von Einem B, Niederschweiberer M, Kalinina S, Walther P, Calzia E, Rueck A, von Arnim CAF (2016)

Event: ADFLIM 2016

Mitochondrial dysfunction is known as an early feature of Alzheimerยดs disease (AD). Amyloid beta (Aฮฒ) as well as its precursor protein APP were identified as key players provoking these mitochondrial disturbances. This entails an energy imbalance in the brain, being one trigger of neuronal death in Alzheimerยดs disease.

To further elucidate the role of the intracellular localization of both proteins in mitochondrial impairment, we performed metabolic characterizations of intact cells overexpressing the respective proteins. Using high-resolution respirometry and electron microscopy, we demonstrate especially the intracellular/mitochondrial pool of Aฮฒ to lower mitochondrial respiration. As the toxic potential of intracellular Aฮฒ underlines the rational of a selective vulnerability of different cell types to Aฮฒ-induced mitochondrial defects, we established a multimodal optical system to measure cell metabolism on the single cell level. Relying on NADH fluorescence lifetime imaging microscopy (NADH FLIM), here we demonstrate that our optical metabolic imaging system is able to mirror the results obtained in the Oroboros Oxygraph-2k and in surplus displays subcellular resolution representing mitochondrial and neuronal heterogeneity in AD.

Our results demonstrate the importance of assessing energy metabolism on the single cell level to shed light onto Alzheimerยดs disease associated mitochondrial dysfunction, highlighting the potential of NADH FLIM for metabolic characterization.


โ€ข O2k-Network Lab: DE Ulm Radermacher P


Labels: MiParea: Respiration  Pathology: Alzheimer's  Stress:Mitochondrial disease 

Tissue;cell: Nervous system  Preparation: Intact cells 



HRR: Oxygraph-2k 


Affiliations

1-Inst Neurology, 2-Central Facility Electron Microscopy, 3-Inst Anรคsthesiolog Pathophysiol Verfahrensentwicklung, 4-Core Facility Confocal Multiphoton Microscopy; Ulm University, Germany. - [email protected]

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