Meeting report of the fifth annual workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer's Disease Research

Abstract

The fifth annual workshop on Principles and Techniques for Improving Preclinical Translation of Alzheimer's Disease Research was held in May 2023 at The Jackson Laboratory in Bar Harbor, Maine, USA. The workshop was established in 2018 to address training gaps in preclinical translational studies for Alzheimer's disease (AD). In addition to providing fundamental knowledge and hands-on skills essential for executing rigorous in vivo studies that are designed to facilitate translation, each year the workshop aims to provide insight on state-of-the-field technological advances and new resources including novel animal models, publicly available datasets, novel biomarkers, and new medical imaging tracers. This innovative and comprehensive workshop continues to deliver training for the greater AD research community in order to provide investigators and trainees with the knowledge and skillsets essential for enabling improved preclinical to clinical translation and accelerate the process of advancing safe and effective therapeutic interventions for AD. HIGHLIGHTS: Translational research is not typically available as a course of study at academic institutions, yet there are fundamental skillsets and knowledge required to enable successful translation from preclinical experiments to clinical efficacy. It is important that there are resources and opportunities available to researchers planning preclinical translational experiments. Here we present proceedings from the fifth annual NIA-sponsored workshop focused on enabling improved preclinical to clinical translation for Alzheimer's disease research that includes didactic lectures on state-of-the-field approaches and hands-on practicums for acquiring essential translational laboratory techniques.

Keywords: Alzheimer's disease; best practices; mouse models; preclinical translation; rigor and reproducibility; training.

FIGURE 1

Precision translational medicine approach used by the Model Organism for the Evaluation of Late Onset Alzheimer's Disease (MODEL‐AD) consortium's Preclinical Testing Core and the Target Enablement to Accelerate Therapy Development for AD (TREAT‐AD) consortium for selecting the most appropriate mouse model matched for a drug's mechanism of action. Midkine (MDK) is an example of a target being pursued for the treatment of AD with small molecule inhibitors. Mouse models are selected based on recapitulation of human AD disease signatures at both the molecular (mult‐omic) level based on transcriptomic and proteomic data, and based on presence of AD‐related pathology and biomarkers (fluid, imaging). Exploration of the AD Knowledge Portal and MODEL‐AD Explorer data resources identified aged 5XFAD mice as a model that recapitulates MDK signatures in AD patients., Aβ, amyloid beta; PD, pharmacodynamics; PK, pharmacokinetics; PET, positron emission tomography.

FIGURE 2

The Model Organism for the Evaluation of Late Onset Alzheimer's Disease (MODEL‐AD) consortium's Preclinical Testing Core drug screening pipeline is a resource available to the greater research community with a priori go/no‐go decision points that prioritize translational outcomes to permit unbiased rigorous drug screening. API, active pharmaceutical ingredient; CSF, cerebrospinal fluid; EEG, electroencephalography; IU, Indiana University; JAX, The Jackson Laboratory; LOAD, late onset Alzheimer's disease; PD, pharmacodynamics; PITT, University of Pittsburgh; PK, pharmacokinetics; STOP‐AD, Selecting The Optimal Pharmaceutical for preclinical drug testing in AD.