Phospholipid composition and levels are not altered in fibroblasts bearing presenilin-1 mutations.
Lipid alterations have been reported in brain regions affected by Alzheimer disease (AD). The mechanisms causing these changes are poorly understood because it is difficult to study dynamic, biochemical processes in post-mortem brain. Fibroblasts derived from AD patients offer an alternative model to study disease-related alterations in lipid metabolism. Therefore, we measured the phospholipid levels and composition of fibroblasts from individuals 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 ratio were not different between presenilin-1 mutation bearing and control fibroblasts. Although these presenilin-1 mutation bearing fibroblasts have a number of biochemical changes related to AD, the absence of a change in phospholipid levels suggests that under these conditions, these cells are not useful in studying the mechanisms underlying the alterations in brain phospholipid 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 these fibroblasts under different conditions.
Murphy
E J
EJ
Section on Brain Physiology and Metabolism, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. murphye@mail.nih.gov
Zhang
H
H
Sorbi
S
S
Rapoport
S I
SI
Gibson
G E
GE
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism; D005192:Family Health; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism*; D010955:Plasmalogens / Q000032:analysis / Q000378:metabolism; D017354:Point Mutation; D053764:Presenilin-1
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010743:Phospholipids; D010955:Plasmalogens; D053764:Presenilin-1; D002784:Cholesterol