Mitochondrial dysfunction in Alzheimer’s disease - a proteomics perspective

ABSTRACT

Mitochondrial dysfunction is involved in Alzheimer’s disease (AD) pathogenesis. Mitochondria have their own genetic material; however, most of their proteins (∼99%) are synthesized as precursors on cytosolic ribosomes, and then imported into the mitochondria. Therefore, exploring proteome changes in these organelles can yield valuable information and shed light on the molecular mechanisms underlying mitochondrial dysfunction in AD. Here, we review AD-associated mitochondrial changes including the effects of amyloid beta and tau protein accumulation on the mitochondrial proteome. We also discuss the relationship of ApoE genetic polymorphism with mitochondrial changes, and present a meta-analysis of various differentially expressed proteins in the mitochondria in AD.

Area covered: Proteomics studies and their contribution to our understanding of mitochondrial dysfunction in AD pathogenesis.

Expert opinion: Proteomics has proven to be an efficient tool to uncover various aspects of this complex organelle, which will broaden our understanding of mitochondrial dysfunction in AD. Evidently, mitochondrial dysfunction is an early biochemical event that might play a central role in driving AD pathogenesis.

KEYWORDS:

• Proteomics
• Alzheimer’s disease
• Mitochondrial dysfunction

Article highlights

• Proteomics is an efficient tool to unravel the abnormalities in mitochondrial machinery in AD.

• Mitochondria are the major target of beta-amyloid (Aβ) and tau protein toxicity.

• Mitochondrial failure is an early event in AD progression; a compensatory response ensues in response to early molecular changes in AD

• Mitochondrial protein perturbations can be considered as potential biomarkers for early AD diagnosis.

• Gender and genetic factors are potential drivers of mitochondrial dysfunction in AD.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary Material

Supplemental data for this article can be accessed here

Additional information

Funding

We acknowledge funding support from the National Health and Medical Research Council (NHMRC) of Australia, the Hilcrest Foundation, the Ophthalmic Research Institute of Australia (ORIA), and Macquarie University, NSW, Australia.