Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer's disease (AD). We investigated the involvement of phospholipase D (PLD) in the pathophysiology of AD. We showed dramatic upregulation of PLD1 immunoreactivity in reactive astroglial cells in brain tissue sections from authentic AD patients. Expression and activity of PLD1 were up-regulated in brain tissues from AD patients, especially caveolae membrane fraction, compared with those of control brains. Interestingly, PLD1 physically interacts and colocalizes with APP and caveolin-3. We found that APP was associated with the pleckstrin homology domain of PLD1, and the amyloid region of APP interacted with PLD. Elevated expression of APP stimulated PLD activity in human astroglioma cells. These results suggest that up-regulation of PLD might have a role in the neuronal pathology associated with AD.
|Number of pages
|Neurobiology of Aging
|Published - 2007 Jul
Bibliographical noteFunding Information:
This study was supported by grant No. R01-2006-000-10521-0 (2006) from the Basic Research Program of the Korea Science & Engineering Foundation and by the Biotechnology Development Program (grant number 2005-00115) from Ministry of Science and Technology (MOST), Korea and grant of the Korea Health 21 R&D project, Ministry of Health and Welfare, Republic of Korea (A020007). A total of six post-mortem brain specimens of Alzheimer's disease patients and age-matched controls were obtained from the IBR Brain Bank (Dr. Piotr B. Kozlowski, who is head of New York IBR brain bank and co-author of this manuscript). So, we used post-mortem brain specimens of Alzheimer's disease patients according to appropriate approval and procedure.
All Science Journal Classification (ASJC) codes
- General Neuroscience
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology