title: Insights into mitochondrial dysfunction: aging, amyloid-β, and tau-A deleterious trio.
abstract: CONCLUSIONS
  Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder mainly affecting elderly individuals. The pathology of AD is characterized by amyloid plaques (aggregates of amyloid-β [Aβ]) and neurofibrillary tangles (aggregates of tau), but the mechanisms underlying this dysfunction are still partially unclear.
  
  
  BACKGROUND
  A growing body of evidence supports mitochondrial dysfunction as a prominent and early, chronic oxidative stress-associated event that contributes to synaptic abnormalities and, ultimately, selective neuronal degeneration in AD.
  
  
  RESULTS
  In this review, we discuss on the one hand whether mitochondrial decline observed in brain aging is a determinant event in the onset of AD and on the other hand the close interrelationship of this organelle with Aβ and tau in the pathogenic process underlying AD. Moreover, we summarize evidence from aging and Alzheimer models showing that the harmful trio "aging, Aβ, and tau protein" triggers mitochondrial dysfunction through a number of pathways, such as impairment of oxidative phosphorylation (OXPHOS), elevation of reactive oxygen species production, and interaction with mitochondrial proteins, contributing to the development and progression of the disease.
  
  
  CONCLUSIONS
  The aging process may weaken the mitochondrial OXPHOS system in a more general way over many years providing a basis for the specific and destructive effects of Aβ and tau. Establishing strategies involving efforts to protect cells at the mitochondrial level by stabilizing or restoring mitochondrial function and energy homeostasis appears to be challenging, but very promising route on the horizon.
authors: Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Basel, Switzerland.
authors: Karen
authors: K
authors: Schmitt
authors: Amandine
authors: A
authors: Grimm
authors: Anna
authors: A
authors: Kazmierczak
authors: Joanna B
authors: JB
authors: Strosznajder
authors: Jürgen
authors: J
authors: Götz
authors: Anne
authors: A
authors: Eckert
mesh_terms: D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species; D016875:tau Proteins