1. A novel process driving Alzheimer's disease validated in a mousemodel: Therapeutic potential.
- Author
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Greenfield, Susan A., Cole, Gregory M., Coen, Clive W., Frautschy, Sally, Singh, Ram P., Mekkittikul, Marisa, Garcia-Ratés, Sara, Morrill, Paul, Hollings, Owen, Passmore, Matt, Hasan, Sibah, Carty, Nikisha, Bison, Silvia, Piccoli, Laura, Carletti, Renzo, Tacconi, Stephano, Chalidou, Anna, Pedercini, Matthew, Kroecher, Tim, and Astner, Hubert
- Subjects
ALZHEIMER'S disease ,NICOTINIC receptors ,PEPTIDES ,TRANSGENIC mice ,BRAIN diseases - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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