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

• Published in: Neurobiology of aging Vol. 28; no. 7; pp. 1015 - 1027
• Main Authors: Jin, Jae-Kwang, Ahn, Bong-Hyun, Na, Yeo-Jung, Kim, Jae-Il, Kim, Yong-Sun, Choi, Eun-Kyoung, Ko, Young-Gyu, Chung, Kwang Chul, Kozlowski, Piotr B, Min, Do Sik
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2007
• Subjects: Aged; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloid beta-Protein Precursor - pharmacology; Amyloid precursor protein; Animals; Astrocytoma; Blood Proteins - chemistry; Blood Proteins - metabolism; Brain - metabolism; Brain - pathology; Caveolin; Caveolin 3 - metabolism; Cell Line; Cercopithecus aethiops; Female; Humans; Immunoprecipitation - methods; Internal Medicine; Mutagenesis - physiology; Neurology; Phospholipase D; Phospholipase D - metabolism; Phosphoproteins - chemistry; Phosphoproteins - metabolism; Postmortem Changes; Reactive astrocytes; Transfection - methods; Up-Regulation - drug effects; Up-Regulation - physiology; β-Amyloid; ADP-ribosylation factor; APP; MES-buffered saline; neurofibrillary tangles; PX; PLD; phosphate-buffered saline; phenylmethylsulfonyl fluoride; Dulbecco's modified Eagles's medium; caveolin-enriched membrane; Aβ; DMEM; amyloid precursor protein; phosphatidylcholine; Alzheimer's disease; NFT; protein kinase C; phosphatidylbutanol; β-amyloid; MBS; PBS; phospholipase D; AD; TBS; pleckstrin homology; Caveolin; Reactive astrocytes; FAD; PKC; CEM; GFAP; PA; PC; ARF; PMSF; PtdBut; PH; tris-buffered saline; familial Alzheimer's disease; phosphatidic acid; N-terminal phox; glial fibrillary acidic protein; Amyloid precursor protein; Phospholipase D; β-Amyloid
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2006.05.022

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.