Ceramides and sphingomyelinases in senile plaques

• Published in: Neurobiology of disease Vol. 65; pp. 193 - 201
• Main Authors: Panchal, Maï, Gaudin, Mathieu, Lazar, Adina N., Salvati, Elisa, Rivals, Isabelle, Ayciriex, Sophie, Dauphinot, Luce, Dargère, Delphine, Auzeil, Nicolas, Masserini, Massimo, Laprévote, Olivier, Duyckaerts, Charles
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2014; Elsevier
• Subjects: Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - complications; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Analytical chemistry; Apolipoproteins E - genetics; Aβ peptide; Biochemistry; Biochemistry, Molecular Biology; Ceramides; Ceramides - metabolism; Chemical Sciences; Chromatography, Liquid; Female; Genomics; Humans; Laser microdissection; Life Sciences; Lipidomics; Lipids; Male; Mass Spectrometry; Microdissection; Middle Aged; Neurobiology; Neurology; Neurons and Cognition; Plaque, Amyloid - etiology; Plaque, Amyloid - metabolism; Quantitative Methods; Senile plaques; Sphingomyelin Phosphodiesterase - metabolism; Sphingomyelinase; Structural Biology; Surface Plasmon Resonance; LPG; AD; PS; Aβ peptide; Alzheimer disease; Laser microdissection; Lipidomics; Lipids; Aβ; Cer; PC; Senile plaques; LC–MSE; PE; LCM; Ceramides; ApoE; GlcCer; SM; Sphingomyelinase; SP; Mass spectrometry; senile plaque; LC–MS E; glucosyl ceramide; laser capture microdissection; ceramides; phosphatidylserines; A β; Alzheimer's disease; amyloid- β peptide; lysyl-phosphatidylglycerol; phosphatidylethanolamines; phosphatidylcholines; sphingomyelins; liquid chromatography coupled with tandem mass spectrometry; apolipoprotein E
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2014.01.010

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. •The senile plaques are enriched in specific ceramides.•This accumulation of ceramides is not due to their affinity for the aggregated Aβ.•Ceramides seem to be overproduced within the senile plaques.