The mechanisms underlying membrane assembly, and the conditions which affect membrane stability in normal and diseased cells are the principal topics of this project. We have previously reported that the physiological temperature Tp is a critical point for membrane assembly, and that the lipid composition is the principal determinant for the assembly process at Tp. Total lipid extracts of membranes from a wide variety of tissues and cell types exhibit unique physical properties that appear only at an experimental temperature which is identical with the Tp of each of the membranes. In mammals the critical temperatures vary from tissue to tissue and therefore reflect local metabolic contributions to the ambient physiological temperatures. Our measurements on the lipid extracts of mammalian cells indicate that the local temperatures vary significantly. For example, human erthrocyte membranes exibit a value of 37.2 degrees C, while for human brain cortex it is 39.5 degrees C. For diseased tissues we have observed critical temperatures which are significantly below Tp. Such membranes with reduced critical temperatures, in an environment with a higher ambient temperature Tp is intrinsically unstable and the membrane structure will degenerate to a non-biological state. In each case where this has been observed a lipid defect has been found. For Alzheimer's disease post-mortem brain tissue the lipid defect is a deficit in phosphatidylethanolamine plasmalogen (PPE) in mid-temporal cortex with marked neurodegeneration. This decrease in PPE is tissue specific, and we have found that it can account for the entire decrease in critical temperature of the tissue.
