Related Experiment Video
Updated: May 3, 2026
09:09
Preparation of Human Tissues Embedded in Optimal Cutting Temperature Compound for Mass Spectrometry Analysis
Published on: April 27, 2021
2.0K
Ceramides and sphingomyelinases in senile plaques
Maï Panchal1, Mathieu Gaudin2, Adina N Lazar3
1Laboratoire 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.
Neurobiology of Disease
|February 4, 2014
Summary
Alzheimer disease (AD) brain plaques show higher levels of specific saturated ceramides. This accumulation appears to be due to local production, not direct binding to amyloid-beta deposits.
Area of Science:
- Neuroscience
- Biochemistry
- Lipidomics
Background:
- Senile plaques are key pathological hallmarks of Alzheimer disease (AD).
- Understanding the molecular composition of these plaques is crucial for deciphering AD pathogenesis.
- Lipid alterations within the AD brain are increasingly recognized as significant contributors to disease progression.
Purpose of the Study:
- To compare the lipidome of senile plaques with adjacent plaque-free neuropil in Alzheimer disease brains.
- To investigate the potential mechanisms behind ceramide accumulation in senile plaques.
Main Methods:
- Laser microdissection to isolate senile plaques and surrounding neuropil.
- Liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS) for lipidomic analysis.
- Surface plasmon resonance (SPR) and fluorescent microscopy to assess ceramide-Aβ interactions.
Main Results:
- Senile plaques were significantly enriched in saturated ceramides Cer(d18:1/18:0) (33% increase) and Cer(d18:1/20:0) (78% increase) compared to neuropil.
- In vitro studies showed no direct interaction between ceramides and amyloid-beta (Aβ) fibrils.
- Fluorescent ceramides did not show affinity for senile plaques in AD brain tissue.
- Acid and neutral sphingomyelinases, enzymes involved in ceramide production, were detected in the corona of senile plaques.
Conclusions:
- Specific saturated ceramides accumulate in Alzheimer disease senile plaques.
- This accumulation is likely due to local production by sphingomyelinases within the plaque microenvironment, rather than direct binding to Aβ.
- These findings highlight a novel lipid-based mechanism potentially contributing to AD pathology.
Related Concept Videos
01:35Asymmetric Lipid Bilayer
8.0K
Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
8.0K
01:23Alzheimer Disease ll: Pathophysiology
35
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and...
35
01:30Atherosclerosis I: Introduction
2.5K
Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
2.5K
01:32Membrane Lipids
19.6K
Lipids are an essential component of all biological membranes. The average lipid content in mammalian membranes is 50%, though it can be as low as 20% in the inner mitochondrial membrane or as high as 80% in the myelin sheath present around the nerve cells.
Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin are the most common phospholipids present in mammalian membranes. At physiological pH, phosphatidylserine is negatively charged, while the other three...
Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin are the most common phospholipids present in mammalian membranes. At physiological pH, phosphatidylserine is negatively charged, while the other three...
19.6K
03:03Amyloid Fibrils
10.2K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
10.2K
01:27Synthesis of Phosphatidylcholine in the ER Membrane
3.3K
The ER synthesizes lipids for building cell membranes and performing cellular functions such as energy storage and signaling. The lipid synthesis machinery embedded in the ER membrane primarily collects all reactants from the cytosol. Following synthesis, the secretory pathway and the ER contact sites distribute these lipids to other cellular organelles. Additionally, the energy-rich triacylglycerides are transported from the ER via lipid droplets.
The major components of all eukaryotic cell...
The major components of all eukaryotic cell...
3.3K