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Differential gene expression in human brain pericytes induced by amyloid‐β protein
Author(s) -
Rensink A. A. M.,
OtteHöller I.,
Donkelaar H. J. ten,
De Waal R. M. W.,
Kremer B.,
Verbeek M. M.
Publication year - 2004
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2004.00536.x
Subject(s) - cyclin d1 , biology , cerebral amyloid angiopathy , senile plaques , programmed cell death , gene expression , microbiology and biotechnology , pathology , cell cycle , apoptosis , alzheimer's disease , gene , medicine , genetics , dementia , disease
Cerebral amyloid angiopathy is one of the characteristics of Alzheimer's disease (AD) and this accumulation of fibrillar amyloid‐β (Αβ) in the vascular wall is accompanied by marked vascular damage. In vitro , Aβ 1−40 carrying the ‘Dutch’ mutation (DAβ 1−40 ) induces degeneration of cultured human brain pericytes (HBP). To identify possible intracellular mediators of Aβ‐induced cell death, a comparative cDNA expression array was performed to detect differential gene expression of Aβ‐treated vs. untreated HBP. Messenger RNA expression of cyclin D1, integrin β4, defender against cell death‐1, neuroleukin, thymosin β10, and integrin α5 were increased in DAβ 1−40 ‐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 Aβ‐mediated degeneration of cerebrovascular cells. Moreover, cyclin D1 expression, but also that of integrin β4, defender against cell death‐1, neuroleukin and thymosin β10 was found in a subset of senile plaques, suggesting a role for these proteins in the pathogenesis of senile plaques.