title: Mitochondrial dysfunction: cause and consequence of Alzheimer's disease.
abstract: The etiology of common, nonfamiliar late-onset Alzheimer's disease (LOAD) is only partly understood and seems to be extremely complex including many genetic and environmental factors. The most important environmental risk factor to develop LOAD is aging itself. Aging and LOAD are considered to be strongly linked to mitochondrial dysfunction and enhanced oxidative stress. In this review, we focus on the interaction between mitochondrial dysfunction in aging especially on defects of the respiratory chain of the oxidative phosphorylation system resulting in enhanced oxidative stress and the interplay between aging-associated mitochondrial defects and LOAD-associated mitochondrial failure. The deleterious effects of the two hallmarks of LOAD, amyloid beta, and hyperphosphorylated tau, on mitochondrial function, movement, and morphology are described as well as the toxic effects of the most relevant genetic risk factor of LOAD, the apolipoprotein E4 allele. Finally, the review provides an overview about drugs and nutritional ingredients which improve mitochondrial function or/and act as antioxidants and discusses their potential role in the treatment of LOAD.
authors.affiliation: Molecular and Clinical Pharmacy, Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Friedland-Leuner
authors.affiliation: Department of Pharmacology, Biocenter, University of Frankfurt, Frankfurt, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Stockburger
authors.affiliation: Molecular and Clinical Pharmacy, Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Henriette Schmidt-Burkhardt Chair of Food Chemistry, Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Denzer
authors.affiliation: Department of Pharmacology, Biocenter, University of Frankfurt, Frankfurt, Germany.
authors.forename: Gunter P
authors.initials: GP
authors.lastname: Eckert
authors.affiliation: Department of Pharmacology, Biocenter, University of Frankfurt, Frankfurt, Germany.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D010085:Oxidative Phosphorylation
chemical_list: D000975:Antioxidants
keywords: Fission; Fusion; Reactive oxygen species; Respiratory chain; mtDNA