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F5‐04‐02: Anti‐Aβ immunotherapy results in a dramatic shift in the inflammatory profile: Implications for amyloid reductions and vascular complications
Author(s) -
Wilcock Donna
Publication year - 2011
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.2011.05.2344
Subject(s) - inflammation , microglia , medicine , immunization , immunology , immunotherapy , immune system
II injections began. Once again hypertensive mice had a significant increase in microglia and astrocytes activation, an increase in CAA and total cerebral Ab in the Tg2576 mice. The final experiment was conducted in 24 months old mice with a less aggressive chronic angiotensin II plus L-NAME protocol. However we terminated the experiment at 14 days due to loss of mice. As observed in the previous experiment, the Tg2576 mice began to develop clinical symptoms of stroke at 5 days while the non-Tg mice only began to show symptoms at day 15. Both non-Tg and Tg2576 mice displayed increased microglia and astrocyte activation when compared to the PBS control mice. Because of the extensive cerebral Ab deposition in the 25 months old Tg2576 mice we were not able to detect a significant difference in CAA, Ab plaque load or Ab ELISA measurements between the hypertensive and the PBS control Tg2576 mice. Conclusions: Tg2576 mice are much more prone to develop ICHs in response to hypertension than the non-Tg littermates. Moreover, there was robust glial activation and increase in CAA in the gray matter of Tg2576 mice showing that hypertension may affect gray as well as white matter in the brain. Importantly, even moderate hypertension for one month in young (12 months) Tg2576 mice increased neuroinflammation, CAA and parenchymal Ab. Further studies may provide insights into the hypertension-induced changes in the cerebral vascular system that initiated the increase in CAA. The accumulation of Ab in the cerebrovascular system is a significant risk factor for intracerebral hemorrhage (ICH), and has been linked to endothelial transport failure and blockage of perivascular drainage. While management of hypertension and atherosclerosis can reduce the incidence of ICH, there are currently no approved therapies for attenuating CAA. Thus there is a critical need for new strategies that improve BBB function and limit the development of beta-amyloidosis in the cerebral vasculature.