Immunotherapy of cerebrovascular amyloidosis in a transgenic mouse model |
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Authors: | Lifshitz Veronica Weiss Ronen Benromano Tali Kfir Einat Blumenfeld-Katzir Tamar Tempel-Brami Catherine Assaf Yaniv Xia Weiming Wyss-Coray Tony Weiner Howard L Frenkel Dan |
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Affiliation: | a Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel b Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA c Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA |
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Abstract: | Cerebrovascular amyloidosis is caused by amyloid accumulation in walls of blood vessel walls leading to hemorrhagic stroke and cognitive impairment. Transforming growth factor-β1 (TGF-β1) expression levels correlate with the degree of cerebrovascular amyloid deposition in Alzheimer's disease (AD) and TGF-β1 immunoreactivity in such cases is increased along the cerebral blood vessels. Here we show that a nasally administered proteosome-based adjuvant activates macrophages and decreases vascular amyloid in TGF-β1 mice. Animals were nasally treated with a proteosome-based adjuvant on a weekly basis for 3 months beginning at age 13 months. Using magnetic resonance imaging (MRI) we found that while control animals showed a significant cerebrovascular pathology, proteosome-based adjuvant prevents further brain damage and prevents pathological changes in the blood-brain barrier. Using an object recognition test and Y-maze, we found significant improvement in cognition in the treated group. Our findings support the potential use of a macrophage immunomodulator as a novel approach to reduce cerebrovascular amyloid, prevent microhemorrhage, and improve cognition. |
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Keywords: | Cerebrovascular disease Cognitive impairment Intracerebral hemorrhage Macrophage MRI Vaccine Therapy |
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