PHOSPHOLIPID-METABOLIZING ENZYMES IN ALZHEIMERS-DISEASE - INCREASED LYSOPHOSPHOLIPID ACYLTRANSFERASE ACTIVITY AND DECREASED PHOSPHOLIPASE A(2) ACTIVITY

Damage to brain membrane phospholipids may play an important role in t he pathogenesis of Alzheimer's disease (AD); however, the critical met abolic processes responsible for the generation and repair of membrane phospholipids affected by the disease are unknown, We measured the ac tivity of key phospholipid catabolic and anabolic enzymes in morpholog ically affected and spared areas of autopsied brain of patients with A D and in matched control subjects. The activity of the major catabolic enzyme phospholipase A(2) (PLA(2)), measured in both the presence and absence of Ca2+ was significantly decreased (-35 to -53%) in parietal and temporal cortices of patients with AD. In contrast, the activitie s of lysophospholipid acyltransferase, which recycles lysophospholipid s into intact phospholipids, and glycerophosphocholine phosphodiestera se, which returns phospholipid catabolites to be used in phospholipid resynthesis, were increased by similar to 50-70% in the same brain are as. Brain activities of enzymes involved in de novo phospholipid synth esis (ethanolamine kinase, choline kinase, choline phosphotransferase, phosphoethanolamine cytidylyltransferase, and phosphocholine cytidyly ltransferase) were either normal or only slightly altered, The activit ies of PLA(2) and acyltransferase were normal in the degenerating cere bellum of patients with spinocerebellar atrophy type 1, whereas the ac tivity of glycerophosphocholine phosphodiesterase was reduced, suggest ing that the alterations in AD brain were not nonspecific consequences of neurodegeneration. Our data suggest that compensatory phospholipid metabolic changes are present in AD brain that reduce the rate of pho spholipid loss via both decreased catabolism (PLA(2)) and increased ph ospholipid resynthesis (acyltransferase and glycerophosphocholine phos phodiesterase).