PHOSPHOLIPID METABOLITE LEVELS ARE ALTERED IN CEREBRAL-CORTEX OF PATIENTS WITH DOMINANTLY INHERITED OLIVOPONTOCEREBELLAR ATROPHY

We measured metabolic precursors and breakdown products of phosphatidy lcholine (choline, glycerophosphocholine (GPC)) and phosphatidyl-ethan olamine (ethanolamine, glycerophosphoethanolamine (GPE)) as well as th e amino acid serine, a precursor of phosphatidylserine, in four morpho logically unaffected cerebral cortical areas obtained at autopsy from 14 patients with dominantly inherited olivopontocerebellar atrophy (OP CA) and 13 controls matched for age and postmortem interval. As compar ed with the controls, mean GPE levels were elevated by 49-57% in front al and parietal cortices of OPCA brains whereas concentrations of etha nolamine were significantly reduced in temporal, occipital and parieta l cortex (-40 to -54%). This resulted in increased GPE/ethanolamine ra tios (+80 to +146%). GPC levels were significantly increased (by 53%) in the frontal cortex of OPCA patients relative to controls. Free seri ne levels were reduced by 20 to 28% in frontal, parietal, temporal, an d occipital cortices. These abnormalities in phospholipid metabolite l evels in OPCA resemble those seen in Alzheimer's disease, although the changes in GPC are less pronounced. These changes in phospholipid met abolism in OPCA cerebral cortex, a brain area spared from neurodegener ative changes, points to generalized disturbances in cellular membrane function in this disease.