title: Neuronal apoptosis in Alzheimer's disease: the role of age-related mitochondrial metabolic competence.
abstract: To assess the role of the mitochondrial metabolic competence (MMC) in the development of age-related changes, we measured the levels of immunohistochemically stained (IH) mitochondrial- and nuclear-encoded subunits of cytochrome oxidase (COX II and COX IV, respectively) and compared these data with mRNA in situ hybridization (ISH) of the same subunits and with cytochemically evidenced COX activity in the temporal (TC) and frontal (FC) cortex of adult and late-adult monkeys. Quantitative cytochemistry of COX activity was performed by calculating the ratio (R) of the area of the cytochemical precipitate to the area of the respective organelle. Although ISH studies showed reduced gene expression of both subunits in FC of late-adult monkeys, no significant age-related difference was found either in TC or FC when considering the IH data. R was significantly increased in FC of late-adult animals, and a quartile distribution of the mitochondrial area showed that R is higher in the FC of older animals independent of the organelle size. The assessment of COX genetic and phenotypic parameters reliably reports on MMC because this enzyme is the terminal complex of the electron transport chain. Taken together, the present IH, ISH, and R findings suggest that, with advancing age, compensating mechanisms are activated to preserve the mitochondrial functional metabolic capacities. Although significant mitochondrial defects are currently reported to occur in Alzheimer's disease pathogenesis, our data document that MMC is actively involved in the physiological rearrangement of the age-related neuronal network and may provide substantial metabolic support for the energy demand of neuronal apoptosis.
authors.affiliation: Neurobiology of Aging Laboratory, Italian National Research Center on Aging, Ancona, Italy. c.bertoni@inrca.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Bertoni-Freddari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fattoretti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Casoli
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Stefano
authors.forename: Marta
authors.initials: M
authors.lastname: Balietti
authors.forename: Belinda
authors.initials: B
authors.lastname: Giorgetti
authors.forename: Gemma
authors.initials: G
authors.lastname: Perretta
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005625:Frontal Lobe / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008252:Macaca fascicularis; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D013702:Temporal Lobe / Q000201:enzymology
chemical_list: D003576:Electron Transport Complex IV