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Updated: May 3, 2026
Using Isolated Mitochondria from Minimal Quantities of Mouse Skeletal Muscle for High throughput Microplate Respiratory Measurements
Published on: October 30, 2015
Mitochondrial oxygen consumption deficits in skeletal muscle isolated from an Alzheimer's disease-relevant murine
Rosemary A Schuh1, Kathryn C Jackson, Anna E Schlappal
1Research Service, VAMHCS, 10 North Greene Street, 3C-125, Baltimore, Maryland 21201, USA. rschu003@umaryland.edu.
Background:
Age is considered a primary risk factor for neurodegenerative diseases including Alzheimer's disease (AD). It is also now well understood that mitochondrial function declines with age. Mitochondrial deficits have been previously assessed in brain from both human autopsy tissue and disease-relevant transgenic mice. Recently it has been recognized that abnormalities of muscle may be an intrinsic aspect of AD and might contribute to the pathophysiology. However, deficits in mitochondrial function have yet to be clearly assessed in tissues outside the central nervous system (CNS). In the present study, we utilized a well-characterized AD-relevant transgenic mouse strain to assess mitochondrial respiratory deficits in both brain and muscle. In addition to mitochondrial function, we assessed levels of transgene-derived amyloid precursor protein (APP) in homogenates isolated from brain and muscle of these AD-relevant animals.
Results:
We now demonstrate that skeletal muscles isolated from these animals have differential levels of mutant full-length APP depending on muscle type. Additionally, isolated muscle fibers from young transgenic mice (3 months) have significantly decreased maximal mitochondrial oxygen consumption capacity compared to non-transgenic, age-matched mice, with similar deficits to those previously described in brain.
Conclusions:
This is the first study to directly examine mitochondrial function in skeletal muscle from an AD-relevant transgenic murine model. As with brain, these deficits in muscle are an early event, occurring prior to appearance of amyloid plaques.
Insights
Mitochondrial dysfunction occurs early in Alzheimer's disease (AD) muscle, mirroring brain deficits, even before amyloid plaques form. This study reveals early muscle abnormalities in an AD mouse model.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Aging Research
Background:
- Age is a primary risk factor for Alzheimer's disease (AD).
- Mitochondrial function declines with age and is impaired in AD brains.
- Muscle abnormalities may contribute to AD pathophysiology, but mitochondrial function in non-CNS tissues is understudied.
Purpose of the Study:
- To assess mitochondrial respiratory function and amyloid precursor protein (APP) levels in brain and skeletal muscle of an AD-relevant transgenic mouse model.
- To investigate whether mitochondrial deficits observed in AD brain are also present in peripheral tissues like muscle.
Main Methods:
- Utilized a well-characterized AD-relevant transgenic mouse strain.
- Assessed mitochondrial respiratory function in isolated muscle fibers.
- Measured levels of transgene-derived APP in brain and muscle homogenates.
Main Results:
- Skeletal muscles showed differential levels of mutant full-length APP based on muscle type.
- Young transgenic mice (3 months) exhibited significantly decreased maximal mitochondrial oxygen consumption in muscle fibers compared to controls.
- These mitochondrial deficits in muscle were comparable to those previously observed in the brain.
Conclusions:
- This is the first study to directly assess mitochondrial function in skeletal muscle of an AD-relevant transgenic mouse model.
- Mitochondrial deficits in muscle are an early pathological event in this AD model, preceding amyloid plaque formation.
- Findings suggest peripheral muscle abnormalities may be an intrinsic aspect of AD.
