期刊
NEUROBIOLOGY OF DISEASE
卷 65, 期 -, 页码 193-201出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2014.01.010
关键词
Alzheimer disease; Senile plaques; Laser microdissection; Lipidomics; Mass spectrometry; Ceramides; Lipids; A beta peptide; Sphingomyelinase
资金
- Ministry of Health PHRC (France)
- France Alzheimer Patients Association
- ANR (French-Canadian Cooperation) [Cho1AD]
- France Alzheimer
- France Parkinson
- ARSEP
- Connaitre les Syndromes Cerebelleux
- Fondation pour la Recherche Medicale
- Region-Ile-de-France
- Centre National de la Recherche Scientifique
- Technologie Servier (Orleans, France)
- program Investissements d'avenir [ANR-10-IAIHU-06]
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.
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