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P2‐342: The influence of chronic cerebral hypoperfusion on Alzheimer‐like pathology in 3xTg mice
Author(s) -
Scullion Gillian A.,
Coltman Robin,
Fowler Jill,
Horsburgh Karen
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.1393
Subject(s) - perfusion , pathology , medicine , hippocampus , amyloid (mycology) , senile plaques , cortex (anatomy) , white matter , cerebral cortex , cerebral hypoperfusion , alzheimer's disease , neuroscience , biology , magnetic resonance imaging , disease , radiology
mutation of human APP, were exposed by the VEGF receptor antagonist and inhibitor of angiogenesis, SU5416, and the effects of SU5416 on APP metabolism were examined. Results: Exposure of primary neuronal cells by SU5416 for 24 hours resulted in increased release of sAPPb, and strikingly enhanced secretion of Ab(1-40) and Ab(1-42) into the culture medium, which was accompanied by a significant increase in b-secretase activity, as compared to control incubations. In contrast, incubation of primary astrocytes in the presence of SU5416 for 24h resulted in decreased secretion of Ab(1-40) and Ab(1-42), and sAPPb into the culture medium, as compared to control incubations. The SU5416-induced effects on APP processing could not be suppressed by the additional presence of VEGF, sugesting that SU5416 affects pathways that are apparently independent of VEGF receptor signaling. Conclusions: The data obtained indicate that the angiogenesis inhibitor SU5416 may affect APP processing but differentially acting in neurons and astrocytes.The data further suggest a link of angiogenesis and pathogenesis of Alzheimer’s disease.