Phospholipase D1 is up-regulated in the mitochondrial fraction from the brains of Alzheimer's disease patients.

Mitochondrial dysfunction may play an important role in sporadic Alzheimer's disease (AD) progression. Recently, we have reported that amyloid precursor protein (APP) stimulates phospholipase D (PLD) activity and beta-amyloid (Abeta) region of APP is involved in the interaction with PLD1. To elucidate the involvement of PLD in the pathophysiology of AD, we examined the expression of PLD1 and alteration of membrane phospholipid in mitochondrial membranes of control and AD brains using Western blot and phospholipid analysis by thin layer chromatography (TLC). We have found that protein expression of PLD1 was significantly increased in mitochondrial fraction of brains of AD patients compared with that in control brains. Furthermore, the concentration of mitochondrial phospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was increased and the content of phosphatidic acid (PA), a product of PLD activity, was up-regulated in the mitochondrial membrane fractions of AD brain compared with that of control brain. These results suggest that up-regulation of PLD1 in the mitochondrial fraction of AD brain might affect the composition of membrane phospholipids and provide a clue to the mechanism underlying the mitochondrial dysfunction associated with AD.