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Mitochondrial Alterations in Peripheral Mononuclear Blood Cells from Alzheimer's Disease and Mild Cognitive
A Delbarba1, G Abate2, C Prandelli2
1Diadem Ltd., Spin Off of Brescia University, Brescia, Italy.
Abstract:
It is well recognized that mitochondrial dysfunction contributes to neurodegeneration occurring in Alzheimer's disease (AD). However, evidences of mitochondrial defects in AD peripheral cells are still inconclusive. Here, some mitochondrial-encoded and nuclear-encoded proteins, involved in maintaining the correct mitochondria machine, were investigated in terms of protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs) isolated from AD and Mild Cognitive Impairment (MCI) patients and healthy subjects. In addition mitochondrial DNA copy number was measured by real time PCR. We found some differences and some similarities between AD and MCI patients when compared with healthy subjects. For example, cytochrome C and cytochrome B were decreased in AD, while MCI showed only a statistical reduction of cytochrome C. On the other hand, both AD and MCI blood cells exhibited highly nitrated MnSOD, index of a prooxidant environment inside the mitochondria. TFAM, a regulator of mitochondrial genome replication and transcription, was decreased in both AD and MCI patients' blood cells. Moreover also the mitochondrial DNA amount was reduced in PBMCs from both patient groups. In conclusion these data confirmed peripheral mitochondria impairment in AD and demonstrated that TFAM and mtDNA amount reduction could be two features of early events occurring in AD pathogenesis.
Insights
Peripheral mitochondrial impairment is confirmed in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). Reduced TFAM (transcription factor A, mitochondrial) and mitochondrial DNA (mtDNA) levels may indicate early AD pathogenesis.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Biochemistry
Background:
- Mitochondrial dysfunction is a known contributor to neurodegeneration in Alzheimer's disease (AD).
- Evidence of mitochondrial defects in peripheral cells of AD patients remains inconclusive.
- Investigating peripheral cells offers a potential window into systemic disease processes.
Purpose of the Study:
- To investigate mitochondrial protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs) from AD and Mild Cognitive Impairment (MCI) patients.
- To assess mitochondrial DNA (mtDNA) copy number in PBMCs from AD and MCI patients.
- To identify potential peripheral biomarkers for early AD pathogenesis.
Main Methods:
- Protein expression and enzymatic activity assays were performed on PBMCs from AD, MCI, and healthy subjects.
- Mitochondrial DNA copy number was quantified using real-time PCR.
- Specific mitochondrial proteins (cytochrome C, cytochrome B, MnSOD, TFAM) were analyzed.
Main Results:
- Cytochrome C and B levels were decreased in AD PBMCs; only cytochrome C was reduced in MCI PBMCs.
- Both AD and MCI PBMCs showed increased nitration of MnSOD, indicating mitochondrial oxidative stress.
- TFAM levels and mtDNA copy number were reduced in PBMCs from both AD and MCI patients compared to controls.
Conclusions:
- Peripheral mitochondria are impaired in AD patients.
- Reduced TFAM and mtDNA levels in PBMCs may serve as early indicators of AD pathogenesis.
- These findings highlight the potential of peripheral blood cells as a diagnostic tool for neurodegenerative diseases.
