The Core was designed to screen compounds for their ability to reduce brain interstitial fluid (ISF) Aβ levels. Brain ISF can be sampled hourly in living mice using microdialysis. The technique not only determines the magnitude that a compound alters ISF Aβ, but also the kinetics of that change.
Services
Determine the effect of compounds on ISF Aβ levels in living mice. Compounds can be administered directly to the brain via the microdialysis probe, injected intraperitoneal or subcutaneous, or given orally. Brain ISF Aβ levels are typically sampled in 1 hour increments over 36-48 hours. Each mouse can receive a single dose, a gradual escalation of several doses, or can receive several distinct compounds.
Measures
Aβ40 and Aβ42 can be measured by sandwich ELISA.
Other analytes can also be measured within the microdialysis samples. For example, compounds levels can be assessed to determine brain exposure following systemic administration.
Animal Models
APP transgenic mice (Tg2576, PS1/APP), wildtype mice, or other mouse models that can be provided by user. Microdialysis is typically performed in mice that do not contain Aβ deposition (ie plaques), however when necessary studies can also be performed in mice with Aβ pathology.
Usage
The Aβ Microdialysis Core is available to both academic groups and corporate groups. Contact us below to discuss experimental design. Each study can be tailored to test the specific type of compound.
Contact
John R. Cirrito, Ph.D., Core Director
Email: cirritoj@neuro.wustl.eduThis email address is being protected from spam bots, you need Javascript enabled to view it
Phone: 314-362-1610
Support
The Core is supported by Cure Alzheimer’s Fund and an anonymous foundation.
Select Aβ Microdialysis References
Cirrito JR, et al. (2003). In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J Neuroscience 23:8844-53.
Cirrito JR, et al. (2005). P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model. J Clinical Investigation 115: 3285-90.
Cirrito JR, et al. (2005). Synaptic Activity Regulates Interstitial Fluid Amyloid-beta Levels In Vivo. Neuron 48:913-922.
Cirrito JR, et al. (2008). Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo. Neuron 58: 42-51.