Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6810048 | Neurobiology of Aging | 2012 | 13 Pages |
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.
Keywords
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Biochemistry, Genetics and Molecular Biology
Ageing
Authors
Veronica Lifshitz, Ronen Weiss, Tali Benromano, Einat Kfir, Tamar Blumenfeld-Katzir, Catherine Tempel-Brami, Yaniv Assaf, Weiming Xia, Tony Wyss-Coray, Howard L. Weiner, Dan Frenkel,