Ceramides and sphingomyelinases in senile plaques

被引:50
作者
Panchal, Mai [1 ,2 ]
Gaudin, Mathieu [3 ,4 ]
Lazar, Adina N. [1 ,2 ,5 ]
Salvati, Elisa [6 ,7 ]
Rivals, Isabelle [8 ]
Ayciriex, Sophie [3 ]
Dauphinot, Luce [2 ]
Dargere, Delphine [3 ]
Auzeil, Nicolas [3 ]
Masserini, Massimo [6 ,7 ]
Laprevote, Olivier [3 ,9 ]
Duyckaerts, Charles [1 ,2 ,5 ]
机构
[1] Hop La Pitie Salpetriere, AP HP, Lab Neuropathol Escourolle, F-75651 Paris 13, France
[2] UPMC, INSERM UMR S 975, CNRS UMR 7225, Ctr Rech ICM, F-75654 Paris 13, France
[3] Univ Paris 05, PRES Sorbonne Paris Cite, Fac Sci Pharmaceut & Biol, EA 4463, Paris, France
[4] Technol Servier, Div Metab, Orleans, France
[5] UPMC Paris Univ, Paris, France
[6] Univ Milano Bicocca, Dept Hlth Sci, Monza, Italy
[7] Univ Milano Bicocca, Nanomed Ctr, Monza, Italy
[8] ESPCI Paris Tech, Equipe Stat Appl, Paris, France
[9] Hop Lariboisiere, AP HP, Lab Toxicol Biol, F-75475 Paris, France
关键词
Alzheimer disease; Senile plaques; Laser microdissection; Lipidomics; Mass spectrometry; Ceramides; Lipids; A beta peptide; Sphingomyelinase; ALZHEIMERS-DISEASE; AMYLOID-BETA; SPHINGOLIPID METABOLISM; APOLIPOPROTEIN-E; CHOLESTEROL; BRAIN; INVOLVEMENT; ASSOCIATION; EXPRESSION; APOPTOSIS;
D O I
10.1016/j.nbd.2014.01.010
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The senile plaque is a hallmark lesion of Alzheimer disease (AD). We compared, without a priori, the lipidome of the senile plaques and of the adjacent plaque-free neuropil. The analysis by liquid chromatography coupled with electrospray ionization mass spectrometry revealed that laser microdissected senile plaques were enriched in saturated ceramides Cer(d18:1/18:0) and Cer(d18:1/20:0) by 33 and 78% respectively with respect to the surrounding neuropil. This accumulation of ceramides was not explained by their affinity for A beta deposits: no interaction between ceramide-liposomes and A beta fibrils was observed in vitro by surface plasmon resonance and fluorescent ceramide-liposomes showed no affinity for the senile plaques in AD brain tissue. Accumulation of ceramides could be, at least partially, the result of a local production by acid and neutral sphingomyelinases that we found to be present in the corona of the senile plaques. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:193 / 201
页数:9
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