Ceramides and sphingomyelinases in senile plaques.
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 Aβ deposits: no interaction between ceramide-liposomes and Aβ 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.
Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, Paris, France; Centre de recherche de l'ICM, UPMC, INSERM UMR S 975, CNRS UMR 7225, France.
Maï
M
Panchal
Chimie-Toxicologie Analytique et Cellulaire, EA 4463, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, PRES Sorbonne Paris Cité, France; Division Métabolisme, Technologie Servier, Orléans, France.
Mathieu
M
Gaudin
Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, Paris, France; Centre de recherche de l'ICM, UPMC, INSERM UMR S 975, CNRS UMR 7225, France; Equipe de Statistique Appliquée, ESPCI Paris Tech, Paris, France. Electronic address: adina_m31@yahoo.com.
Adina N
AN
Lazar
UPMC Paris Universitas, France.
Elisa
E
Salvati
Department of Health Sciences and Nanomedicine Center, University of Milano Bicocca, Monza, Italy.
Isabelle
I
Rivals
Chimie-Toxicologie Analytique et Cellulaire, EA 4463, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, PRES Sorbonne Paris Cité, France.
Sophie
S
Ayciriex
Centre de recherche de l'ICM, UPMC, INSERM UMR S 975, CNRS UMR 7225, France.
Luce
L
Dauphinot
Chimie-Toxicologie Analytique et Cellulaire, EA 4463, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, PRES Sorbonne Paris Cité, France.
Delphine
D
Dargère
Chimie-Toxicologie Analytique et Cellulaire, EA 4463, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, PRES Sorbonne Paris Cité, France.
Nicolas
N
Auzeil
UPMC Paris Universitas, France.
Massimo
M
Masserini
Chimie-Toxicologie Analytique et Cellulaire, EA 4463, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, PRES Sorbonne Paris Cité, France; Laboratoire de Toxicologie Biologique, Hôpital Lariboisière, AP-HP, Paris, France.
Olivier
O
Laprévote
Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, Paris, France; Centre de recherche de l'ICM, UPMC, INSERM UMR S 975, CNRS UMR 7225, France; Equipe de Statistique Appliquée, ESPCI Paris Tech, Paris, France.
Charles
C
Duyckaerts
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D002518:Ceramides / Q000378:metabolism*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D042282:Microdissection; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000209:etiology / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D002518:Ceramides; D013108:Sphingomyelin Phosphodiesterase
Alzheimer disease; Aβ peptide; Ceramides; Laser microdissection; Lipidomics; Lipids; Mass spectrometry; Senile plaques; Sphingomyelinase