Evidence for a membrane defect in Alzheimer disease brain.
To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.
Nitsch
R M
RM
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Blusztajn
J K
JK
Pittas
A G
AG
Slack
B E
BE
Growdon
J H
JH
Wurtman
R J
RJ
D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001923:Brain Chemistry; D002794:Choline / Q000378:metabolism; D004314:Down Syndrome / Q000378:metabolism; D005997:Glycerylphosphorylcholine / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism
D008563:Membrane Lipids; D010743:Phospholipids; D010767:Phosphorylcholine; D005997:Glycerylphosphorylcholine; D010727:Phosphoric Diester Hydrolases; C061931:glycerophosphocholine cholinephosphodiesterase; D002794:Choline