Related Experiment Video
Updated: Jul 7, 2026

Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models
Published on: June 30, 2023
Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice
S Hauptmann1, I Scherping, S Dröse
1Department of Pharmacology, ZAFES, Biocenter, University of Frankfurt, 60438 Frankfurt, Germany.
Abstract:
Recent evidence suggests mitochondrial dysfunction as a common early pathomechanism in Alzheimer's disease integrating genetic factors related to enhanced amyloid-beta (Ass) production and tau-hyperphosphorylation with aging, as the most relevant sporadic risk factor. To further clarify the synergistic effects of aging and Ass pathology, we used isolated mitochondria of double Swedish and London mutant APP transgenic mice and of non-tg littermates. Pronounced mitochondrial dysfunction in adult Thy-1 APP mice, such as a drop of mitochondrial membrane potential and reduced ATP-levels already appeared at 3 months when elevated intracellular but not extracellular Ass deposits are present. Mitochondrial dysfunction was associated with higher levels of reactive oxygen species, an altered Bcl-xL/Bax ratio and reduction of COX IV activity. We observed significant decreases in state 3 respiration and FCCP-uncoupled respiration in non-tg mice after treatment with extracellular Ass. Similar deficits were seen only in aged Thy-1 APP mice, probably due to compensation within the respiratory chain in young animals. We conclude that Ass dependent mitochondrial dysfunction starts already at 3 months in this AD model before extracellular deposition of Ass and progression accelerates substantially with aging.
Related Concept Videos
Alzheimer Disease l: Introduction
Alzheimer Disease ll: Pathophysiology
Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Dementia l: Introduction
Mitochondria
