Alzheimer’s Disease Research Studies
Current therapies for Alzheimer’s disease (AD) primarily target tau and beta amyloid (Aβ) peptides. These therapies include inhibitors to reduce tau protein phosphorylation and BACE inhibitors to reduce Aβ levels. Aβ antibodies are also used to sequester free Aβ from plasma for clearance by the immune system. The development of effective AD therapies is very challenging, and few compounds have shown significant benefits in clinical trials, primarily due to the lack of druggable targets and reliable biomarkers.
At Charles River, Alzheimer’s disease drug discovery services include end-to-end capabilities across the drug discovery continuum. Our target discovery and validation tools include cell-based phenotypic screens and RNAi and CRISPR screening services in physiologically relevant cell lines such as iPS-derived neurons, ES cells, and rodent primary cell lines. Additionally, we have unique access to human AD post-mortem brain tissues allowing assays on patient-derived cells that help expedite your Alzheimer’s disease research.
There are several animal models of Alzheimer’s research that are used for pharmacology and efficacy studies. At Charles River, we have performed studies on Tg2576 and CVN transgenic mouse models, which display pathologies associated with Alzheimer’s disease. Additionally, we have aged rat and mouse models as well as amnesia models to perform cognitive neuroscience studies and test pathological changes associated with AD. The AD mouse models have been validated using multiple endpoints such as:
- Behavior efficacy and phenotyping
- Sensory motor function
- Gait and balance changes
- Cognitive changes
- Social interaction
- T2-MRI for volumetric analysis
- Proton magnetic resonance spectroscopy (1H-MRS)
- Pharmacological MRI
- Biomarkers identification
- Immunohistochemistry of amyloid plaques, phosphorylated Tau, GFAP, Iba1 and other markers
- BrdU incorporation as a measure of cell proliferation
- Cytokine expression
- Soluble Amyloid beta peptide measurement
- Neurochemical profiling by microdialysis (ACh, 5HT, NE, DA, Glu and other metabolites)
- Microdialysis sampling and bioanalysis for PK studies
More recently, we have extended our AD drug discovery services to include large animal models that are used to study higher cognitive function and changes. Our large animal models are evaluated using a broad range cognitive test battery that is similar to the CANTAB touchscreen testing methods used in humans.
Have additional questions? Check out our Alzheimer’s disease studies FAQs page for more information.