Table of Contents
Neurodegeneration is a central feature of many rodent models of CNS diseases. The ability to accurately and robustly measure neurodegeneration and its modulation by therapeutic intervention can be a powerful tool in preclinical studies of experimental disease-modifying therapies.
Example methods to measure neurodegeneration in rodent models
- Quantitative measures on tissue sections
- Morphological measures
- Immunohistochemistry & immunofluorescence markers
- Fluid-based biomarkers
- Neurofilament Light (NfL) in plasma & CSF
- Non-invasive imaging
- MRI-derived volume and cortical thickness measures
Quantitative Measures on Tissue Sections
Manual measurement of cortical thickness on a mouse brain tissue section.
Counting or density measures based on immunohistochemistry (IHC) stained tissue sections using cell body, dendritic, axonal, and/or synaptic markers. Example of NeuN IHC staining in an alpha-synuclein preformed fibril (PFF) seeding/spreading model of Parkinson's disease demonstrating clear neuronal loss in the ipsilateral piriform cortex of mice injected with PFFs in the anterior olfactory nucleus (AON).
Fluid-based Biomarkers
Quantitative analysis of neurofilament light (NfL) in the plasma of PBS and PFF inoculated mice measured by the Simoa assay. This example demonstrates highly elevated levels of NfL at 12 and 16 weeks post-inoculation in this model.
Non-invasive Imaging
Automated measurement of regional brain volumes from anatomical MR images. This example shows segmentation (red) of the piriform cortex in a control mouse (left) compared to an synuclein PFF-injected mouse with significant atrophy of the cortex ipsilateral to the injection site (right).