Damage to brain membrane
phospholipids may play an important role in the pathogenesis of
Alzheimer's disease (AD); however, the critical metabolic processes responsible for the generation and repair of membrane
phospholipids affected by the disease are unknown. We measured the activity of key
phospholipid catabolic and anabolic
enzymes in morphologically affected and spared areas of autopsied brain of patients with AD and in matched control subjects. The activity of the major catabolic
enzyme phospholipase A2 (PLA2), 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 activities of
lysophospholipid acyltransferase, which recycles
lysophospholipids into intact
phospholipids, and
glycerophosphocholine phosphodiesterase, which returns
phospholipid catabolites to be used in
phospholipid resynthesis, were increased by approximately 50-70% in the same brain areas. Brain activities of
enzymes involved in de novo
phospholipid synthesis (
ethanolamine kinase,
choline kinase,
choline phosphotransferase,
phosphoethanolamine cytidylyltransferase, and
phosphocholine cytidylyltransferase) were either normal or only slightly altered. The activities of PLA2 and
acyltransferase were normal in the degenerating cerebellum of patients with
spinocerebellar atrophy type 1, whereas the activity of
glycerophosphocholine phosphodiesterase was reduced, suggesting 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
phospholipid loss via both decreased catabolism (PLA2) and increased
phospholipid resynthesis (
acyltransferase and
glycerophosphocholine phosphodiesterase).