Phospholipase D1 is associated with amyloid precursor protein in Alzheimer's disease.

Abstract

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.

• Authors: Jae-Kwang Jin, Bong-Hyun Ahn, Yeo-Jung Na, Jae-Il Kim, Yong-Sun Kim, Eun-Kyoung Choi, Young-Gyu Ko, Kwang Chul Chung, Piotr B Kozlowski, Do Sik Min
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 28 Issue 7 Pg. 1015-27 (Jul 2007) ISSN: 1558-1497 [Electronic] United States
• PMID: 16797788 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Protein Precursor
• Blood Proteins
• Caveolin 3
• Phosphoproteins
• platelet protein P47
• Phospholipase D
• phospholipase D1

Topics

• Aged
• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Protein Precursor (genetics, metabolism, pharmacology)
• Animals
• Astrocytoma
• Blood Proteins (chemistry, metabolism)
• Brain (metabolism, pathology)
• Caveolin 3 (metabolism)
• Cell Line
• Chlorocebus aethiops
• Female
• Humans
• Immunoprecipitation (methods)
• Mutagenesis (physiology)
• Phospholipase D (metabolism)
• Phosphoproteins (chemistry, metabolism)
• Postmortem Changes
• Transfection (methods)
• Up-Regulation (drug effects, physiology)