title: Differential gene expression in human brain pericytes induced by amyloid-beta protein.
abstract: 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.
authors.affiliation: Department of Neurology, University Medical Centre, Nijmegen, the Netherlands.
authors.forename: A A M
authors.initials: AA
authors.lastname: Rensink
authors.forename: I
authors.initials: I
authors.lastname: Otte-Höller
authors.forename: H J
authors.initials: HJ
authors.lastname: ten Donkelaar
authors.forename: R M W
authors.initials: RM
authors.lastname: De Waal
authors.forename: B
authors.initials: B
authors.lastname: Kremer
authors.forename: M M
authors.initials: MM
authors.lastname: Verbeek
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins