Related Experiment Video
Updated: May 6, 2026
Author Spotlight: Decoding Mitochondrial Aging
Published on: June 30, 2023
Mitochondrial alterations near amyloid plaques in an Alzheimer's disease mouse model
Hong Xie1, Jisong Guan, Laura A Borrelli
1MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, Massachusetts 02129 and School of Life Sciences, Tsinghua University, 100084 Beijing, China.
Abstract:
While accumulation of amyloid-β (Aβ) deposited as senile plaques is a hallmark feature of Alzheimer's disease (AD), the neurotoxicity of these deposits remains controversial. Recent in vitro studies suggested a link between elevated Aβ and mitochondrial dysfunction that might contribute to the pathogenesis of AD. However, the in vivo evidence for mitochondria dysfunction caused by Aβ is still missing. Using intravital multiphoton imaging with a range of fluorescent markers, we systematically surveyed mitochondrial structural and functional changes in AD mouse models. We observed severe impairments to be limited to the vicinity of Aβ plaques, which included reduction of both numbers and membrane potential of mitochondria and the emergence of dystrophic and fragmented mitochondria. Both neuronal soma and neurites with oxidative stress show severe alterations in mitochondrial membrane potential in amyloid precursor protein mice. These results provide in vivo evidence revealing Aβ plaques as focal sources of toxicity that lead to severe structural and functional abnormalities in mitochondria. These alterations may contribute to neuronal network dysfunction and warrant further investigation as possible targets for therapeutic intervention in AD.
Insights
Alzheimer's disease amyloid-β plaques cause localized mitochondrial dysfunction in vivo. This study provides evidence of impaired mitochondria near plaques, suggesting a therapeutic target for Alzheimer's disease.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Amyloid-β (Aβ) plaque accumulation is a hallmark of Alzheimer's disease (AD).
- The in vivo neurotoxicity of Aβ, particularly its effect on mitochondria, remains unclear.
- Previous in vitro studies suggested a link between Aβ and mitochondrial dysfunction.
Purpose of the Study:
- To investigate the in vivo effects of Aβ plaques on mitochondrial structure and function in Alzheimer's disease models.
- To determine if Aβ deposits are focal sources of mitochondrial toxicity.
Main Methods:
- Intravital multiphoton imaging was employed in AD mouse models.
- A range of fluorescent markers were used to assess mitochondrial structural and functional changes.
- Mitochondrial number, membrane potential, and morphology were systematically surveyed.
Main Results:
- Severe mitochondrial impairments were observed in the vicinity of Aβ plaques.
- Reductions in mitochondrial number and membrane potential were noted.
- Dystrophic, fragmented mitochondria and oxidative stress were evident in neurons and neurites near plaques.
Conclusions:
- Aβ plaques act as focal sources of toxicity, causing significant mitochondrial abnormalities in vivo.
- These mitochondrial dysfunctions may contribute to neuronal network dysfunction in Alzheimer's disease.
- Targeting these Aβ-induced mitochondrial alterations presents a potential therapeutic strategy for AD.
Related Concept Videos
01:23Alzheimer Disease ll: Pathophysiology
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...