Mitochondrial Alterations in Peripheral Mononuclear Blood Cells from Alzheimer’s Disease and Mild Cognitive Impairment Patients

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.

Modified level of miR‐376a is associated with Parkinson's disease

“…Consistent with our result, as reported by Delbarba et al, AD PBMCs show a significant decrease in PGC1α expression, while PCG1α was unchanged in mild cognitive impairment (MCI) patients. Additionally, the expression of TFAM dropped in PBMCs derived from both AD and MCI patients . In addition, to the best of our knowledge, this is the first study reporting alterations in PGC1α , and TFAM levels in peripheral cells of parkinsonian patients.…”

“…There is a substantial literature indicating possible links between PGC1α and diverse neurodegenerative diseases (NDDs), comprising amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD) and PD . As a target gene of PGC1α, TFAM regulates mitochondrial genome replication and transcription as well as mitochondrial biogenesis . TFAM also makes a positive contribution to mtDNA stability and initiates synthesis of mtDNA‐encoded respiratory chain subunits .…”

“…Since maintenance of mitochondrial machinery depends on the action of some mitochondria‐related nuclear‐encoded proteins, the principal aim of this study was to assess the expression levels PGC1α, TFAM and GSK3β, as well as their predicted upstream miRNA, miR‐376a, in chronic and acute models of PD and patient's peripheral blood mononuclear cells (PBMCs).…”

Alzheimer’s Disease: Molecular Hallmarks and Yeast Models

“…Many investigators have suggested that epigenetic changes in the copy numbers of mtDNA and mtDNA mutations might be involved in AD pathogenesis [60][61][62][63][64][65]. However, the analysis of the literature reveals the existence of inconsistent findings and methodological shortcomings affecting a large proportion of mtDNA association studies on AD [66][67][68][69].…”

Role of Stress, Immune System and Well-being in Patients with Alzheimer's Disease

“…Moreover, it was seen that there is a tendency in the group of participants without AD since, when cortisol increases, there is a decrease in IgA in saliva, while in AD participants, when cortisol increases, the IgA level in saliva increases too. All of these changes can be explained due to cellular, molecular and physiological changes in the organism that are also related to the mood of patients [13][14][15].…”