Mitochondrial dysfunction - the beginning of the end in Alzheimer's disease? Separate and synergistic modes of tau and amyloid-β toxicity

By Anne Eckert, K. Schmitt, Jürgen Götz. Alzheimer's Research & Therapy, 2011

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The pathology of Alzheimer's disease (AD) is characterized by amyloid plaques (aggregates of amyloid-β (Aβ)) and neurofibrillary tangles (aggregates of tau) and is accompanied by mitochondrial dysfunction, but the mechanisms underlying this dysfunction are poorly understood. In this review, we discuss the critical role of mitochondria and the close inter-relationship of this organelle with the two main pathological features in the pathogenic process underlying AD. Moreover, we summarize evidence from AD post-mortem brain as well as cellular and animal AD models showing that Aβ and tau protein trigger mitochondrial dysfunction through a number of pathways, such as impairment of oxidative phosphorylation, elevation of reactive oxygen species production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. A vicious cycle as well as several vicious circles within the cycle, each accelerating the other, can be drawn, emphasizing the synergistic deterioration of mitochondria by tau and Aβ.

Subfields: Molecular Biology, Pharmacology, Physiology

View Paper: https://www.semanticscholar.org/paper/0c09ba03c459b5b6d7a87c54b52874116fed288f

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