Change the Course of Alzheimer’s Disease Research
Take a fresh approach to your Alzheimer’s Disease research with optimized in vitro and in vivo models and assays that provide actionable data to drive your drug development from early discovery through late-stage preclinical. Start with any of our cell-based models, transgenic mouse models, aged rat and mouse models, and amnesia models which display pathologies associated with Alzheimer’s Disease (AD). Keep going and breakthrough with our advanced platform of neuroscience translational tools and assays. From cognitive neuroscience studies to AD-associated pathology, get the data you need with our most advanced neurological imaging techniques, behavioral testing platforms and electrophysiology tools.
Alzheimer's Disease Research Tools
- Sensory motor function
- Gait and balance changes
- Cognitive changes
- Social interaction
- T2-MRI for volumetric analysis
- Proton magnetic resonance spectroscopy (1H-MRS)
- Pharmacological MRI
- 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
- Quantification of biomarkers, amyloid plaques and neuron counts by Stereology
In Vitro Cell-based Assays
The proper combination of Alzheimer’s disease in vitro assays can deliver critical information delivering insights that serve as better predictors for the transition to in vivo studies. Improve your in vivo success by integrating translational cell-based assays from simple cell proliferation and viability assays to multicellular biochemical and functional assays for high content phenotypic screening using our unique access to Alzheimer’s Disease relevant human primary cells from tissue, blood and differentiated stem cells into your AD discovery program.
Transgenic Mouse Models
The Tg2576 Alzheimer's Disease model overexpress this mutant form of amyloid precursor protein. The 5xFAD mouse model expresses human APP and PSEN1 transgenes with a total of five AD-linked mutations. Both available models are validated using multiple endpoints including cognitive testing, measurement of the levels of soluble and insoluble beta amyloid, and biomarker measurement using immunohistochemical staining.
Scopolamine-induced Amnesia Model
Disruption of the cholinergic system leads to amnesia or memory loss. This Alzheimer’s animal study employs Scopolamine, a muscarinic cholinergic receptor antagonist providing a validated animal model to study impaired learning and memory in Alzheimer’s Disease research.
- Large Animal Models
How robust is the CVN model in touch touchscreen testing often used in Alzheimer’s Disease Research?
The CVN mice show statistically significant impairment compared to wild type even though the difference is not very large (10–15%). Having two CVN mice cohorts—a vehicle-treated group and a compound-treated group—would ensure that the phenotype of impaired cognition is reproduced in the vehicle-treated CVN mice. This would result in a reproducible reversal learning graph. The reversal learning (visual discrimination) resembles dimensional human touchscreen testing tasks that are commonly used to assess cognitive impairment so the similarity between rodent touchscreen testing and human touchscreen testing increases the translational index.
Which behavioral deficits are reproducible in CVN mice and are the deficits responsive to Alzheimer’s Disease therapies?
In CVN mice, the motor deficit is reproducible but is used more as a biomarker endpoint and less to assess efficacy. The cognitive deficit is also reproducible and is used more to assess efficacy in Alzheimer’s Disease research using fear conditioning, the Barnes maze or the radial arm water maze. Unfortunately, while the CVN mice have been used extensively, the deficit response to several neuroprotective drugs has not been very successful.
Has Charles River tested therapeutic compounds for Alzheimer’s disease in CVN mice?
In the CVN Alzheimer’s animal model we are testing several options including treating the animals and then performing electrophysiology tests, and using compounds to study differential effects on synaptic transmission in wild-type versus diseased animals.
Are there non-rodent models available for Alzheimer’s Disease research studies?
Large animals have been used to assess cognition using touchscreen technologies. Either aged or scopolamine-treated animals (to impair cognition) are used for touchscreen and biomarker assessment of cerebrospinal fluid (CSF).
Is there a benefit to using the radial arm water maze instead of the standard reference Morris water maze in Alzheimer’s Disease research?
No. One test does not have a significant benefit over the other and both tests are run routinely.
For electrophysiology studies related to Alzheimer’s Disease research, which parameters would you recommend be investigated?
We suggest not only looking at long-term potentiation but also at the amplitude of basal synaptic transmissions. In Alzheimer’s Disease models, the basal synaptic transmission tends to get disrupted, making it easier to detect those changes compared to long-term potentiation changes.
Is it necessary to have a high sample number in Alzheimer’s Disease Research Studies to address the variability that can cause an impact on statistical significance in drug testing studies?
No. In multiple blind studies, we have found similar results in small and large groups of mice.