Intranasal amyloid model of Alzheimer's disease - potential opportunities and challenges

Pharmacol Rep. 2025 Jan 8. doi: 10.1007/s43440-024-00692-4. Online ahead of print.

Abstract

Amyloid beta 1-42 (Aβ1-42) peptide is one of the most studied disease-related amyloidogenic peptides implicated in the pathophysiology of Alzheimer's disease (AD). Despite significant scientific breakthroughs in the recent past, the existing non-transgenic animal models do not demonstrate accurate pathology of AD progression. This review has presented a concise mechanistic understanding of the intranasal amyloid-based animal model of AD, along with its advantages, challenges, and major limitations. Furthermore, discussions on how to combat these challenges to pave the road toward developing novel therapeutics for AD, have also been included. Preclinical exploration of repeated intranasal amyloid-beta exposure would certainly aid the translational development of a robust animal model of AD. This will also provide a better understanding of disease progression and pathology in the intranasal animal model.

Keywords: Alzheimer’s disease; Amyloid beta; Animal models; Intranasal route; Sporadic Alzheimer’s disease.

Publication types

  • Review