UC Irvine

Enhancer-driven adeno-associated viral (AAV) reporters provide compact tools for targeting genetically defined neuronal populations, but their behavior in aging and Alzheimer's disease model contexts remains uncertain. This thesis evaluated four enhancer-AAV reporter datasets in young wild-type, aged wild-type, and 5xFAD mice: BiCHATe27 for cholinergic neurons, BiPVe3 for PV basket cells, BiPVe4 for PV chandelier cells, and BiSSTe4 for SST Martinotti cells. Cleared brain tissue was imaged by light-sheet microscopy and analyzed within paper-matched regions of interest. Reporter-marker specificity, sensitivity, reporter intensity, and raw cell-count burden were interpreted as descriptive pilot readouts. Corrected BiCHATe27 ChAT analysis, driven by marker-appropriate image-analysis changes rather than by a new imaging modality, restored young wild-type targeting estimates close to the AAV toolbox reference and suggested broadly stable targeting with reduced signal burden in aged and 5xFAD samples. BiPVe3, BiPVe4, and BiSSTe4 showed lower or more variable targeting, including scan-quality and ROI-sensitivity effects. Whole-section pathology images added tissue context but were not used for specificity, sensitivity, or plaque-proximity calculations. Overall, the dataset supports a cautious cell-type/subtype-dependent model that requires manual counting, atlas registration, direct amyloid-pathology assessment, and chromatin-accessibility validation before stronger disease-level interpretation.