Brain transit and ameliorative effects of intranasally delivered anti-amyloid-β oligomer antibody in 5XFAD mice

Chun Xiao, Francesca J. Davis, Balwantsinh C. Chauhan, Kirsten L. Viola, Pascale N. Lacor, Pauline T. Velasco, William L. Klein, Neelima B. Chauhan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Alzheimer's disease (AD) is a global health crisis with limited treatment options. Despite major advances in neurotherapeutics, poor brain penetration due to the blood-brain barrier continues to pose a big challenge in overcoming the access of therapeutics to the central nervous system. In that regard, the non-invasive intranasal route of brain targeting is gaining considerable attention. The nasal mucosa offers a large surface area, rapid absorption, and avoidance of first-pass metabolism increasing drug bioavailability with less systemic side effects. Intranasal delivery is known to utilize olfactory, rostral migratory stream, and trigeminal routes to reach the brain. This investigation confirmed that intranasal delivery of oligomeric amyloid-β antibody (NU4) utilized all three routes to enter the brain with a resident time of 96 hours post single bolus intranasal administration, and showed evidence of perikaryal and parenchymal uptake of NU4 in 5XFAD mouse brain, confirming the intranasal route as a non-invasive and efficient way of delivering therapeutics to the brain. In addition, this study demonstrated that intranasal delivery of NU4 antibody lowered cerebral amyloid-β and improved spatial learning in 5XFAD mice.

Original languageEnglish (US)
Pages (from-to)777-788
Number of pages12
JournalJournal of Alzheimer's Disease
Volume35
Issue number4
DOIs
StatePublished - 2013

Keywords

  • Alzheimer's immunotherapy
  • amyloid-β oligomer antibody
  • brain transit
  • cerebral amyloid-β immunocytochemistry
  • intranasal delivery
  • olfactory pathway
  • rostral migratory stream pathway
  • spatial acquisition learning
  • trigeminal pathway

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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