A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential

Susan A Greenfield, Gregory M Cole, Clive W Coen, Sally Frautschy, Ram P Singh, Marisa Mekkittikul, Sara Garcia-Ratés, Paul Morrill, Owen Hollings, Matt Passmore, Sibah Hasan, Nikisha Carty, Silvia Bison, Laura Piccoli, Renzo Carletti, Stephano Tacconi, Anna Chalidou, Matthew Pedercini, Tim Kroecher, Hubert AstnerPhilip A Gerrard

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Introduction: The neuronal mechanism driving Alzheimer's disease (AD) is incompletely understood.

Methods: Immunohistochemistry, pharmacology, biochemistry, and behavioral testing are employed in two pathological contexts-AD and a transgenic mouse model-to investigate T14, a 14mer peptide, as a key signaling molecule in the neuropathology.

Results: T14 increases in AD brains as the disease progresses and is conspicuous in 5XFAD mice, where its immunoreactivity corresponds to that seen in AD: neurons immunoreactive for T14 in proximity to T14-immunoreactive plaques. NBP14 is a cyclized version of T14, which dose-dependently displaces binding of its linear counterpart to alpha-7 nicotinic receptors in AD brains. In 5XFAD mice, intranasal NBP14 for 14 weeks decreases brain amyloid and restores novel object recognition to that in wild-types.

Discussion: These findings indicate that the T14 system, for which the signaling pathway is described here, contributes to the neuropathological process and that NBP14 warrants consideration for its therapeutic potential.

Original languageEnglish
Pages (from-to)e12274
JournalAlzheimer’s & Dementia: Translational Research & Clinical Interventions
Volume8
Issue number1
DOIs
Publication statusPublished - 3 Mar 2022

Keywords

  • 5XFAD, acetylcholinesterase, alphaLISA,Alzheimer’s disease,amyloid beta, basal forebrain, Braak stage, cortex, hippocampus, NBP14, novel object recognition, T14

Fingerprint

Dive into the research topics of 'A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential'. Together they form a unique fingerprint.

Cite this