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Membrane instability, plasmalogen content, and Alzheimer's disease
L Ginsberg1, J H Xuereb, N L Gershfeld
1Department of Clinical Neurosciences, Royal Free Hospital School of Medicine, London, England, UK.
Journal of Neurochemistry
|May 29, 1998
Summary
Alzheimer's disease (AD) alters neural membrane lipid composition, decreasing plasmalogen levels. This change lowers the membrane’s critical stability temperature (T*), potentially destabilizing brain cell membranes in AD patients.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Cell membrane bilayer stability is crucial for normal physiological function and depends on lipid composition relative to ambient temperature (Tp).
- Alterations in membrane lipid composition, observed in diseases like Alzheimer's disease (AD), can lead to a shift in the bilayer's critical stability temperature (T*).
- A known lipid defect in AD temporal cortex is a reduced ratio of plasmalogen to nonplasmalogen ethanolamine glycerophospholipids.
Purpose of the Study:
- To confirm and further investigate the inequality T* << Tp in Alzheimer's disease (AD) temporal cortex neural membranes.
- To explore the role of plasmalogen deficiency in altering the critical temperature (T*) of neural membranes in AD.
- To propose a pathogenetic mechanism for membrane destabilization in AD brain.
Main Methods:
- Utilized a new method to determine the critical temperature (T*) of neural membranes from AD temporal cortex.
- Confirmed the inequality T* << Tp in a larger series of AD samples compared to previous studies.
- Experimentally simulated brain membranes with varying plasmalogen/nonplasmalogen ratios to measure T*.
Main Results:
- Confirmed that for AD temporal cortex neural membranes, the critical stability temperature (T*) is significantly lower than the physiological temperature (T* << Tp).
- Demonstrated that plasmalogen deficiency in artificial lipid mixtures simulating brain membranes directly correlates with a decrease in T*.
- Found that T* is highly sensitive to even minor changes in plasmalogen content.
Conclusions:
- The reduced plasmalogen to nonplasmalogen ethanolamine glycerophospholipid ratio in AD brain membranes contributes to a lower critical stability temperature (T*).
- The inequality T* << Tp is a significant finding that may act as a contributory pathogenetic mechanism leading to neural membrane destabilization in Alzheimer's disease.
- Maintaining appropriate lipid composition, particularly plasmalogens, is vital for neural membrane stability.