title: Lewy body pathology is associated with mitochondrial DNA damage in Parkinson's disease.
abstract: Mitochondrial dysfunction has been strongly implicated in the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD), but its relation to protein aggregation is unclear. PD is characterized by synuclein aggregation (i.e., Lewy body [LB] formation). In AD, the abnormal accumulation of tau protein forms neurofibrillary tangles. In this study, we laser-dissected LB-positive and -negative neurons from the substantia nigra of postmortem PD brains, and tau-positive and -negative hippocampal neurons from AD brains. We quantified mitochondrial DNA deletions in relation to the cellular phenotype and in comparison with age-matched controls. Deletion levels were highest in LB-positive neurons of PD brains (40.5 ± 16.8%), followed by LB-negative neurons of PD cases (31.8 ± 14.4%) and control subjects (25.6 ± 17.5%; analysis of variance p < 0.005). In hippocampal neurons, deletion levels were 25%-30%, independent of disease status and neurofibrillary tangles. The presented findings imply increased mitochondrial DNA damage in LB-positive midbrain neurons, but do not support a direct causative link of respiratory chain dysfunction and protein aggregation.
authors.affiliation: Department of Neurology with Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Sarina K
authors.initials: SK
authors.lastname: Müller
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
authors.forename: Christoph
authors.initials: C
authors.lastname: Laub
authors.forename: Tobias
authors.initials: T
authors.lastname: Högen
authors.forename: Falk
authors.initials: F
authors.lastname: Schlaudraff
authors.forename: Birgit
authors.initials: B
authors.lastname: Liss
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.forename: Matthias
authors.initials: M
authors.lastname: Elstner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; C497604:SNCA protein, human; D051844:alpha-Synuclein