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

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

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1015-1027
Number of pages13
JournalNeurobiology of Aging
Volume28
Issue number7
DOIs
Publication statusPublished - 2007 Jul

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Caveolin
  • Phospholipase D
  • Reactive astrocytes
  • β-Amyloid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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