Noradrenergic modulation in Alzheimer's disease
The locus coeruleus is among the earliest sites of pathology in Alzheimer's disease, showing degeneration years before cognitive symptoms emerge. Using mouse models of amyloid and tau pathology together with chemogenetic control of the LC and behavioral testing, we examine how noradrenergic activity interacts with pathology over time, with the longer-term goal of evaluating neuromodulation as a therapeutic strategy.
Nong et al., 2026, Journal of Alzheimer's Disease
Experimental setup. (a) Breeding paradigms to generate experimental animals for the study. (b) Diagram of AAV-mediated Cre-dependent expression of hM3D(Gq) DREADD receptors in the LC of PS19xDbH-Cre mice (top). Diagram of saline injection into the LC of PS19 or WT littermates as a control for surgery (bottom). (c) Histological confirmation of selective expressions of DREADD receptors in LC neurons. Left: an example low-magnification immunofluorescence image of LC showing the spread of the viral vector. Right: high-magnification immunofluorescence images showing the colocalization of DbH and mCherry signals. (d) Timeline of all experiments of the study. Visual schematics of the behavioral assays are illustrated in the inset. Illustration was created in https://biorender.com.