Targeting vascular amyloid in arterioles of alzheimer disease transgenic mice with amyloid β protein antibody-coated nanoparticles

Joseph F. Poduslo, Kristi L. Hultman, Geoffry L. Curran, Gregory M. Preboske, Ryan Chamberlain, Małgorzata Marjańska, Michael Garwood, Clifford R. Jack, Thomas M. Wengenack

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

The relevance of cerebral amyloid angiopathy (CAA) to the pathogenesis of Alzheimer disease (AD) and dementia in general emphasizes the importance of developing novel targeting approaches for detecting and treating cerebrovascular amyloid (CVA) deposits. We developed a nanoparticle-based technology that uses a monoclonal antibody against fibrillar human amyloid-β42 that is surface coated onto a functionalized phospholipid monolayer. We demonstrate that this conjugated nanoparticle binds to CVA deposits in arterioles of AD transgenic mice (Tg2576) after infusion into the external carotid artery using 3 different approaches. The first 2 approaches use a blood vessel enrichment of homogenized brain and a leptomeningeal vessel preparation from thin tangential brain slices from the surface of the cerebral cortex. Targeting of CVA by the antibody-coated nanoparticle was visualized using fluorescent lissamine rhodamine-labeled phospholipids in the nanoparticles, which were compared with fluorescent staining of the endothelial cells and amyloiddeposits using confocal laser scanning microscopy. The third approach used high-field strength magnetic resonance imaging of antibody-coated iron oxide nanoparticles after infusion into the externalcarotid artery. Dark foci of contrast enhancement in cortical arterioles were observed in T2*-weighted images of ex vivo AD mouse brains that correlated histologically with CVA deposits. The targeting ability of these nanoparticles to CVA provides opportunities for the prevention and treatment of CAA.

Original languageEnglish (US)
Pages (from-to)653-661
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume70
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Alzheimer disease
  • Cerebral amyloid angiopathy
  • Cerebrovascular amyloid
  • Confocal laser scanning microscopy
  • Immunotargeted nanoparticles
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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