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

A Delbarba,F Cuetos,C Prandelli,N Arce Varas,M Memo,C Martinez,A Novelli,D Uberti,M Marziano,L Buizza,G Abate,C Lanni

doi:10.1155/2016/5923938

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.

Highlights

Alzheimer’s disease (AD) is the most common form of dementia among the elderly, characterized by progressive memory loss and cognitive decline
peripheral blood mononuclear cells (PBMCs) derived from 20 AD, 24 Mild Cognitive Impairment (MCI) patients and 30 age-matched controls were evaluated by measuring the protein levels of two redox cofactors, involved in the transfer of electrons through electron transport chain (ETC) complexes, and the activity of two enzymes, which gave the efficiency of mitochondrial functionality
Protein levels of cytochrome B (CYT B), a component of respiratory chain complex III [25], and cytochrome C (CYT C), a small heme-protein involved in the transfer of electrons between complexes III and IV [26], were evaluated in the three different groups by ELISA

Summary

Introduction

Alzheimer’s disease (AD) is the most common form of dementia among the elderly, characterized by progressive memory loss and cognitive decline. The beta amyloid cascade theory has dominated thinking and research efforts in the comprehension and cure of this disease [1]. This theory derived largely from the characterization of rare disease-causing mutations in three genes, which code for amyloid-β protein precursor (AβPP), Presenilin 1, and Presenilin 2, all linked to amyloid-β metabolisms [2]. Recent findings suggest that pathological changes that occur in AD brain, such as synapses and neuronal loss, even excess beta amyloid production, could be causally induced by mitochondrial dysfunction and increased oxidative stress [4,5,6,7].

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