Grant: Master's Award: Canada Graduate Scholarships

Global aging predicts a surge in the Alzheimer's disease (AD) continuum, affecting 416 million globally, with 315 million in preclinical stage. Existing treatments manage symptoms, and lack early detection. AD starts earlier than once thought, which provides a uniquely long window for intervention. This study probes the locus coeruleus in emotional memory in pre-tangle tau AD animal model. Aberrant Tau, salient in AD, emerges early in LC, demonstrating neurotoxicity. Tauopathy drives AD dementia, impacting memory, cognition, and emotional regulation. Late-stage AD is linked to emotional deficits, but preclinical manifestation is unclear. Impaired LC function, density, and fiber loss correlate with behavioral deficits, highlighting LC's role. Operating in phasic and tonic firing modes, LC influences learning, memory, stress, and anxiety. Differential firing modulates tau progression, which may be linked to mitochondria dysregulation. Objectives include studying pre-tangle tau and LC hyperactivity on emotional memory, qPCR for gene profiles, and corticosterone for stress. Hypothesized associations between LC activity, impaired memory, anxiety, and enhanced tau pathology drive the study. Mitochondria dysregulation is expected. Method involves infusing TauE14 into LC using a validated rat model of AD, co-infusing channelrhodopsin-2 for LC stimulation. Rats receive phasic or tonic stimulation, with corticosterone collection. Behavioral assessments molecular analyses will be used. Understanding emotional dysregulation in preclinical AD could innovate stress-associated symptom interventions. Implication of mitochondria in LC function and tauopathy urges investigation for AD treatments. This research promises insights into early AD pathology, guiding preclinical interventions.