Immunotherapy of cerebrovascular amyloidosis in a transgenic mouse model

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

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)432.e1-432.e13
JournalNeurobiology of Aging
Volume33
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Cerebrovascular disease
  • Cognitive impairment
  • Intracerebral hemorrhage
  • Macrophage
  • MRI
  • Therapy
  • Vaccine

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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