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Dystrophic neurites of senile plaques in Alzheimer’s disease are deficient in cytochrome c oxidase

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Abstract

Double-labeling immunofluorescence and confocal microscopy have been used to learn about the local relationship between amyloid, mitochondria, and cytochrome c oxidase (COX) in dystrophic neurites of senile plaques in the frontal cortex in Alzheimer's disease (AD). Dystrophic neurites surrounding amyloid plaques are filled with mitochondrial porin-immunoreactive structures. In contrast with tangle-bearing and non-tangle-bearing neurons, which express mitochondrial porin and COX subunit 4, porin-immunoreactive neurites of senile plaques lack COX subunit 4. Parallel western blot studies in mitochondria-enriched fractions of the frontal cortex in the same cases disclosed reduced expression levels of COX, but not of prohibitin, in AD stages VB/C of Braak. Co-localization of porin and lysosomal associated protein 1, as revealed by double-labeling immunofluorescence and confocal microscopy, suggests that mitochondria may be engulfed by lysosomes in dystrophic neurites. These findings support a local link between amyloid deposition, abnormal mitochondria and impaired respiratory chain function (resulting from decrease of COX expression) in dystrophic neurites of senile plaques in AD.

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Acknowledgments

This work was funded by grant PI05/1570 and supported by the European Commission under the Sixth Framework Programme (BrainNet Europe II, LSHM-CT-2004-503039). We wish to thank T Yohannan for editorial advice.

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Authors and Affiliations

  1. Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Facultat de Medicina, Universitat de Barcelona, carrer Feixa LLarga sn, 08907 Hospitalet de LLobregat, Ciberned, Spain

    Esther Pérez-Gracia & Isidre Ferrer

  2. Serveis Científico-Tecnics, Unitat de Biología de Bellvitge, Hospitalet de LLobregat, Hospitalet, Spain

    Benjamín Torrejón-Escribano

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  1. Esther Pérez-Gracia
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  2. Benjamín Torrejón-Escribano
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Correspondence to Isidre Ferrer.

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Pérez-Gracia, E., Torrejón-Escribano, B. & Ferrer, I. Dystrophic neurites of senile plaques in Alzheimer’s disease are deficient in cytochrome c oxidase. Acta Neuropathol 116, 261–268 (2008). https://doi.org/10.1007/s00401-008-0370-6

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  • DOI: https://doi.org/10.1007/s00401-008-0370-6

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