Publication

Differential gene expression in human brain pericytes induced by amyloid-beta protein

Rensink, A. A. M., Otte-Höller, I., ten Donkelaar, H. J., De Waal, R. M. W., Kremer, B. & Verbeek, M. M., Jun-2004, In : Neuropathology and Applied Neurobiology. 30, 3, p. 279-291 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

Cerebral amyloid angiopathy is one of the characteristics of Alzheimer's disease (AD) and this accumulation of fibrillar amyloid-beta (Alphabeta) in the vascular wall is accompanied by marked vascular damage. In vitro, Abeta1-40 carrying the 'Dutch' mutation (DAbeta1-40) induces degeneration of cultured human brain pericytes (HBP). To identify possible intracellular mediators of Abeta-induced cell death, a comparative cDNA expression array was performed to detect differential gene expression of Abeta-treated vs. untreated HBP. Messenger RNA expression of cyclin D1, integrin beta4, defender against cell death-1, neuroleukin, thymosin beta10, and integrin alpha5 were increased in DAbeta1-40-treated HBP, whereas insulin-like growth factor binding protein-2 mRNA expression was decreased. Corresponding protein expression was investigated in AD and control brains to explore a potential role for these proteins in pathological lesions of the AD brain. Cyclin D1 expression was increased in cerebral amyloid angiopathy and cells in a perivascular position, suggesting that the cell cycle may be disturbed during Abeta-mediated degeneration of cerebrovascular cells. Moreover, cyclin D1 expression, but also that of integrin beta4, defender against cell death-1, neuroleukin and thymosin beta10 was found in a subset of senile plaques, suggesting a role for these proteins in the pathogenesis of senile plaques.

Original languageEnglish
Pages (from-to)279-291
Number of pages13
JournalNeuropathology and Applied Neurobiology
Volume30
Issue number3
Publication statusPublished - Jun-2004

    Keywords

  • Alzheimer Disease, Amyloid beta-Peptides, Brain Chemistry, Cells, Cultured, Cerebral Cortex, DNA, Complementary, Fluorescent Antibody Technique, Gene Expression, Humans, Immunohistochemistry, Nerve Tissue Proteins, Oligonucleotide Array Sequence Analysis, Pericytes, Journal Article, Research Support, Non-U.S. Gov't

ID: 41696325