Oral treatment with iododiflunisal delays beta amyloid plaque formation in a transgenic mouse model of Alzheimer Disease: a Longitudinal in vivo molecular imaging study

• DOI: 10.21203/rs.2.23011/v1
• Publication Date: 2020-02-10T16:26:07Z
• Authors: Luka Rejc; Vanessa Gómez-Val...; Xabier Rios; Unai Cossio; Zuriñe Baz; Edurne Mujica; Tiago Giao; Ellen Y Cotrina; Jesús Jiménez-Bar...; Jordi Quintana; Gemma Arsequell; Isabel Cardoso; Jordi Llop
• Keywords: Standardized uptake value; Amyloid beta; Amyloid (mycology)

Abstract Background: Transthyretin (TTR) is a tetrameric, Amyloid-beta (Aβ)-binding protein, which has been shown to reduce Aβ toxicity both in vitro and vivo. The ability of TTR interact with can be enhanced by series small molecules that stabilize its tetrameric form. Because this, stabilizers might act as disease modifying drugs Alzheimer Disease (AD). In this work, we monitored the therapeutic efficacy two stabilizers, iododiflunisal (IDIF) repurposed drug tolcapone, longitudinal assessment deposition an animal model AD using positron emission tomography (PET) [18F]florbetaben. Methods: Mice (AβPPswe/PS1A246E/TTR+/-; n=21) were divided into 3 groups (n=7 per group): (IDIF)-treated, tolcapone-treated non-treated. treatment, administered drinking water at dose 100 mg/Kg/day, was started 5 months age. level assessed ages=5, 9, 11, 14 PET imaging Treatment determined based on radiotracer uptake hippocampus (HIP) cortex (CTX) respect cerebellum (CB) presented standardized value ratios (SUVr). Immunohistochemical (IHC) analysis performed age further support vivo results. Results: SUVr [18F]florbetaben CTX HIP non-treated animals progressively increased from age=5 11 stabilized afterwards. contrast, IDIF-treated remained constant between ages=5 significantly months. At age=11 months, group showed lower values than those obtained for animals. group, time, but rate group. Moderate treatment effect tolcapone suggests different mechanism action IDIF. No significant observed IDIF- or Results IHC matched data age=14 Conclusions: stabilizer IDIF shows good Aβ-protective effect. Nevertheless, levels treated control reached similar end study. Furthermore, differences suggest mechanisms action.