title: Mitochondria, Cybrids, Aging, and Alzheimer's Disease.
abstract: Mitochondrial and bioenergetic function change with advancing age and may drive aging phenotypes. Mitochondrial and bioenergetic changes are also documented in various age-related neurodegenerative diseases, including Alzheimer's disease (AD). In some instances AD mitochondrial and bioenergetic changes are reminiscent of those observed with advancing age but are greater in magnitude. Mitochondrial and bioenergetic dysfunction could, therefore, link neurodegeneration to brain aging. Interestingly, mitochondrial defects in AD patients are not brain-limited, and mitochondrial function can be linked to classic AD histologic changes including amyloid precursor protein processing to beta amyloid. Also, transferring mitochondria from AD subjects to cell lines depleted of endogenous mitochondrial DNA (mtDNA) creates cytoplasmic hybrid (cybrid) cell lines that recapitulate specific biochemical, molecular, and histologic AD features. Such findings have led to the formulation of a "mitochondrial cascade hypothesis" that places mitochondrial dysfunction at the apex of the AD pathology pyramid. Data pertinent to this premise are reviewed.
authors.affiliation: University of Kansas Alzheimer's Disease Center, University of Kansas School of Medicine, Landon Center on Aging, Kansas City, KS, United States. Electronic address: rswerdlow@kumc.edu.
authors.forename: R H
authors.initials: RH
authors.lastname: Swerdlow
authors.affiliation: University of Kansas Alzheimer's Disease Center, University of Kansas School of Medicine, Landon Center on Aging, Kansas City, KS, United States.
authors.forename: S
authors.initials: S
authors.lastname: Koppel
authors.affiliation: University of Kansas Alzheimer's Disease Center, University of Kansas School of Medicine, Landon Center on Aging, Kansas City, KS, United States.
authors.forename: I
authors.initials: I
authors.lastname: Weidling
authors.affiliation: University of Kansas Alzheimer's Disease Center, University of Kansas School of Medicine, Landon Center on Aging, Kansas City, KS, United States.
authors.forename: C
authors.initials: C
authors.lastname: Hayley
authors.affiliation: University of Kansas Alzheimer's Disease Center, University of Kansas School of Medicine, Landon Center on Aging, Kansas City, KS, United States.
authors.forename: Y
authors.initials: Y
authors.lastname: Ji
authors.affiliation: University of Kansas Alzheimer's Disease Center, University of Kansas School of Medicine, Landon Center on Aging, Kansas City, KS, United States.
authors.forename: H M
authors.initials: HM
authors.lastname: Wilkins
mesh_terms: D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial
keywords: Aging; Alzheimer's disease; Bioenergetics cybrids; Mitochondria