A-Z™ AD Drug Discovery Platform

For more than 10 years, Creative Biolabs has provided comprehensive customized solutions to customers worldwide. With state-of-the-art technology and innovative platforms, we deliver the highest quality service using expertise and personalized solutions.

Overview

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes that can lead to dementia. AD animal models may be very useful for studying the pathophysiology of disease and for testing new therapies in preclinical studies. When choosing a model, researchers should consider various factors that may influence the phenotype. They should also consider the timing of the test/treatment animals, as the age at which certain aspects of AD pathology occur in each model is different. A combination of animal and sequential testing in a model system may be more predictive of human efficacy and provide more insight into the range of effects of this agent.

Biomarkers in AD Drug Development

There are five primary types of biomarkers relevant to AD drug development. We offer AD biomarker assays.

• Brain imaging
• Electrophysiologic Measures
• Measurement of prespecified analytes in plasma and cerebrospinal fluid (CSF)
• "Omics" platform with microarray and spectrometry for the determination of multiple genes, proteins, lipids, and metabolites
• Genetics

Models and Assays for AD Preclinical Drug Discovery at Creative Biolabs

• AD In Vitro Disease Models

In vitro tools have particular advantages in assessing some variables of drug metabolism, even when compared to in vivo models. In vitro tools allow for precise cellular exposure to a given drug. 3D culture models are a promising technique to develop more realistic in vitro disease models for CNS drug research and development. 3D in vitro models obtained using PSC-derived cells would provide a realistic platform for toxicity assessments and drug screening applications.

Fig.1 Platform for AD drug screening in a 3D human neural cell culture model of AD.

• AD In Vivo Disease Models

Transgenic and non-transgenic animal models develop synaptic and memory deficits. They are useful for AD drug discovery. Most Tg models are mice, while non-Tg models can also be rats, monkeys, and dogs.

a. Tg models of AD, consisting of single or multi-Tg animals overexpressing APP, PS, and/or Tau mutations.

Mice overexpression of APP (K670N: M671L) and PS1 (M146L) have been widely used to better understand the pathogenic mechanisms of synaptic dysfunction and memory loss in AD and to validate novel therapeutic approaches. These mice presented a robust age Aβ dependent deposition in plaques preceded by an increase of soluble Aβ40 and Aβ42.

b. Non-Tg models obtained by toxins injection in the brain, including direct injection of Aβ or tau, and models of aging.

Non-Tg models for the study of AD have mainly been obtained by injecting Aβ or tau directly into the brain through intraventricular or hippocampal injection. These models allow:

1. Investigate Aβ the effects of tau in animals for which Tg models are not available.
2. Exclude the confounding effects of overexpression of APP and its fragments.
3. Investigate the different roles of Aβ and tau species (monomers vs. oligomers vs. insoluble) at different concentrations.
4. To study the difference between acute and chronic administration.
5. Clarify aspects of the molecular mechanisms underlying Aβ and tau pathology.

Creative Biolabs is a preclinical contract research organization that provides customized services for AD drug discovery. We are unique in that our scientists can solve problems creatively. Please do not hesitate to contact us and our enthusiastic scientists will discuss it with you in detail.