Differential gene expression in human brain pericytes induced by amyloid-beta protein.
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.
Rensink
A A M
AA
Department of Neurology, University Medical Centre, Nijmegen, the Netherlands.
Otte-Höller
I
I
ten Donkelaar
H J
HJ
De Waal
R M W
RM
Kremer
B
B
Verbeek
M M
MM
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*
D016229:Amyloid beta-Peptides; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins