Acceleration of phosphatidylcholine synthesis and breakdown by inhibitors of mitochondrial function in neuronal cells: a model of the membrane defectof Alzheimer's disease

Brain cells in Alzheimer's disease (AD) exhibit a membrane defect character ized by accelerated phospholipid turnover, The mechanism responsible for th is defect remains unknown. Recent studies indicate that impairment of mitoc hondrial function is frequently observed in AD and may be responsible for c ertain aspects of its pathophysiology, We show that when PC12 cells are exp osed to inhibitors of mitochondrial bioenergetics, the turnover of their ma jor membrane phospholipid, phosphatidylcholine, is accelerated, producing a pattern of metabolic changes that mimics that observed in brains of AD pat ients, Abnormalities of mitochondrial function may therefore underlie the m embrane defect in AD.