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Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging reveals cholesterol overload in the cerebral cortex of Alzheimer disease patients

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Abstract

Although cholesterol has been involved in the pathophysiology of Alzheimer disease (AD), its distribution in the cerebral cortex over the course of AD is unknown. We describe an original method to quantify cholesterol distribution using time-of-flight secondary ion mass spectrometry imaging. Cholesterol was unevenly distributed along the cortical thickness, being more abundant close to the white matter, in both control and AD cases. However, the mean cholesterol signal was significantly higher in the lower half of the cortex in AD samples compared to controls. This increase, when converted into cortical layers, was statistically significant for layers III and IV and did not reach significance in layers V + VI, the variability being too high at the interface between grey and white matter. The density of neurofibrillary tangles and of senile plaques was not statistically linked to the abundance of cholesterol. Cholesterol overload thus appears a new and independent alteration of AD cerebral cortex. The structure in which cholesterol accumulates and the mechanism of this accumulation remain to be elucidated.

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Acknowledgments

We thank Dr Véronique Sazdovitch for her help in collecting and analyzing the samples. The help of the technical staff of Escourolle Neuropathology Laboratory is greatly acknowledged. This work was supported by the Agence Nationale de la Recherche (grants ANR-07-NEURO-009-ChoAD, ANR-2010-BLAN-0805-01 and -02 MASS-IMAGE, and ANR-2010-MALZ-10303 CholAD) and a grant from “Projet Hospitalier de Recherche Clinique” (PHRC), project IMAD. The work was partly funded by France-Alzheimer Association (Project: Identification des partenaires moléculaires du peptide Abeta). The human samples were obtained through the Brain Bank GIE NeuroCEB funded by a consortium of Patients’ Associations (France Alzheimer, France Parkinson, CSC, ARSEP Fondation).

Conflict of interest

The authors disclose no conflict of interest.

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Authors and Affiliations

  1. Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, 47 Bd de l’Hôpital, 75013, Paris, France

    Adina N. Lazar, Maï Panchal & Charles Duyckaerts

  2. Centre de Recherche de l’ICM (UPMC, INSERM UMR S 975, CNRS UMR 7225), 47 Bd de l’Hôpital, 75013, Paris, France

    Adina N. Lazar, Maï Panchal, Luce Dauphinot, Catherine Marquer & Charles Duyckaerts

  3. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France

    Claudia Bich, Nicolas Desbenoit, David Touboul & Alain Brunelle

  4. LRTS, IRCM, DSV, Commissariat à l’Énergie Atomique (CEA), BP 6, 18, Route du Panorama, 92265, Fontenay-aux-Roses cedex, France

    Vanessa W. Petit

  5. Laboratoire de Chimie-Toxicologie Analytique et Cellulaire, EA 4463, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France

    Olivier Laprévote

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  1. Adina N. Lazar
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  2. Claudia Bich
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  11. Charles Duyckaerts
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Correspondence to Charles Duyckaerts.

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Lazar, A.N., Bich, C., Panchal, M. et al. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging reveals cholesterol overload in the cerebral cortex of Alzheimer disease patients. Acta Neuropathol 125, 133–144 (2013). https://doi.org/10.1007/s00401-012-1041-1

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