Phospholipid composition and levels are not altered in fibroblasts bearingpresenilin-1 mutations

Lipid alterations have been reported in brain regions affected by Alzheimer disease (AD). The mechanisms causing these changes are poorly understood b ecause it is difficult to study dynamic, biochemical processes in post-mort em brain. Fibroblasts derived from AD patients offer an alternative model t o study disease-related alterations in lipid metabolism. Therefore, we meas ured the phospholipid levels and composition of fibroblasts from individual s bearing two different presenilin-1 mutations and compared these values to appropriate control fibroblasts. There were no differences between groups in phospholipid composition or in individual phospholipid levels, including the plasmalogens. Cholesterol levels and the cholesterol/phospholipid rati o were not different between presenilin-1 mutation bearing and control fibr oblasts. Although these presenilin-1 mutation bearing fibroblasts have a nu mber of biochemical changes related to AD, the absence of a change in phosp holipid levels suggests that under these conditions, these cells are not us eful in studying the mechanisms underlying the alterations in brain phospho lipid levels associated with AD. However, these results do not preclude the possible use of other fibroblasts bearing AD-related mutations, e.g., APP mutations, to examine AD-related changes in brain lipid metabolism, or of t hese fibroblasts under different conditions. (C) 2000 Elsevier Science Inc.