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Targeting Mitochondrial Dysfunction in Alzheimer's Disease Neurons: Lithium Boosts Oxidative Phosphorylation
Benedict C Albensi1,2,3, Aida Adlimoghaddam4,5,6
1Department of Pharmaceutical Sciences, Barry & Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.
Cells
|May 27, 2026
Summary
Low-dose lithium improves mitochondrial function and energy metabolism in Alzheimer
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Alzheimer's disease (AD) involves amyloid beta (Aβ) and neurofibrillary tangles, impacting mitochondrial function.
- While high-dose lithium is a mood stabilizer, low-dose lithium shows neuroprotective effects against AD pathology, cognitive decline, and inflammation.
- Limited research exists on lithium's impact on brain energy metabolism in AD.
Purpose of the Study:
- To investigate the effect of varying lithium doses on mitochondrial function in Alzheimer's disease (AD) neurons.
- To assess lithium's influence on neuronal energy metabolism, including oxygen consumption, ATP production, and oxidative phosphorylation.
Main Methods:
- Primary neuronal cells were isolated from control and 3xTg-AD mice.
- Mitochondrial oxygen consumption rate (OCR), Cytochrome C Oxidase (COX) activity, and total ATP activity were measured.
- Expression of mitochondrial complex proteins involved in oxidative phosphorylation (OXPHOS) was analyzed.
Main Results:
- Lithium treatment significantly increased mitochondrial OCR, COX activity, and total ATP in 3xTg-AD neurons.
- Lithium elevated levels of mitochondrial complex protein subunits (Complex I-V) in AD neurons.
- Lithium did not affect energy metabolism in control neurons, indicating a specific effect on pathological states.
Conclusions:
- Lithium enhances mitochondrial function and bioenergetics in Alzheimer's disease (AD) neurons.
- These findings suggest lithium's potential therapeutic role in managing brain energy dysregulation in AD.
- Neuronal cells represent a key target for lithium-based interventions in early-stage AD treatment.
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