Membrane instability, plasmalogen content, and Alzheimer's disease.

摘要

The normal stability of the cell membrane bilayer depends on its lipid composition being appropriate to the ambient (physiological) temperature, Tp. Membrane lipid composition may be altered by disease such that the bilayer is only stable at a new critical temperature, T*, which may differ from Tp. In Alzheimer's disease (AD) temporal cortex, a defect of lipid composition has previously been identified, namely, a decrease in the ratio of plasmalogen to nonplasmalogen ethanolamine glycerophospholipids. Furthermore, for AD temporal cortex neural membranes, T* Tp, a finding confirmed in the present study in a larger series than previously, using a new method for obtaining T*. This inequality between T* and Tp has been proposed as a putative contributory pathogenetic mechanism leading to membrane destabilisation in AD brain. The plasmalogen deficiency could account for the change in T* in AD, as shown by experiments where T* was measured for artificial lipid mixtures simulating brain membranes with varying plasmalogenonplasmalogen ratios. The critical temperature was found to be very sensitive to small alterations in plasmalogen content.