Phospholipid metabolite levels are altered in cerebral cortex of patients with dominantly inherited olivopontocerebellar atrophy.
We measured metabolic precursors and breakdown products of phosphatidylcholine (choline, glycerophosphocholine (GPC) and phosphatidylethanolamine (ethanolamine, glycerophosphoethanolamine (GPE)) as well as the amino acid serine, a precursor of phosphatidylserine, in four morphologically unaffected cerebral cortical areas obtained at autopsy from 14 patients with dominantly inherited olivopontocerebellar atrophy (OPCA) and 13 controls matched for age and postmortem interval. As compared with the controls, mean GPE levels were elevated by 49-57% in frontal and parietal cortices of OPCA brains whereas concentrations of ethanolamine were significantly reduced in temporal, occipital and parietal cortex (-40 to -54%). This resulted in increased GPE/ethanolamine ratios (+80 to +146%). GPC levels were significantly increased (by 53%) in the frontal cortex of OPCA patients relative to controls. Free serine levels were reduced by 20 to 28% in frontal, parietal, temporal, and occipital cortices. These abnormalities in phospholipid metabolite levels in OPCA resemble those seen in Alzheimer's disease, although the changes in GPC are less pronounced. These changes in phospholipid metabolism in OPCA cerebral cortex, a brain area spared from neurodegenerative changes, points to generalized disturbances in cellular membrane function in this disease.
Nitsch
R M
RM
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Blusztajn
J K
JK
Doyle
F M
FM
Robitaille
Y
Y
Wurtman
R J
RJ
Growdon
J H
JH
Kish
S J
SJ
D000328:Adult; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008566:Membranes / Q000378:metabolism; D009849:Olivopontocerebellar Atrophies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010743:Phospholipids / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
D004983:Ethanolamines; D010743:Phospholipids; D012694:Serine; D002794:Choline