# Effects of Resonance-Frequency Breathing on Preclinical Alzheimer’s Disease Biomarkers and Cognition > **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $308,754 ## Abstract PROJECT SUMMARY The cascade of brain changes involved in Alzheimer’s disease (AD) starts many years before diagnosis, suggesting that earlier interventions will be more successful. Alzheimer’s tau pathology follows a predictable path through the brain, starting with ‘pretangle’ tau in a small brainstem nucleus called the locus coeruleus decades before any diagnosis. Despite its small size, the locus coeruleus controls many aspects of activity in the brain and body. It is the brain’s arousal hub region, integrating all sorts of signals about arousal (e.g., wakefulness, emotion, novelty, stress) and shaping cortical activity to match current demands. Phasic bursts of LC activity promote synaptic plasticity in the hippocampus and help make novel and emotional events memorable. However, during periods of on-going stress or anxiety, the LC fires steadily (tonically), preventing phasic bursts. LC activity patterns may also determine the impact of tau pathology. In rats with pretangle tau in the LC, stimulating the LC steadily increases cell death while stimulating it intermittently reduces the memory impairment and structural degeneration caused by pretangle tau. These findings in rats used invasive procedures to stimulate the LC, but noninvasive methods, such as breathing, can also influence LC activity. In the current R01 revision, we propose adding a task assessing LC responses to novelty to a stage II doubleblinded randomized trial with Black and White American adults aged 50-70 to test whether daily sessions involving breathing at around the baroreflex frequency (~10 s per breath, known as resonance frequency breathing) affects LC function. The baroreflex provides a negative feedback loop to maintain blood pressure at nearly constant levels. Elevated blood pressure stretches mechanical baroreceptors in arterial walls which signal the brainstem, causing the heart rate to decrease and blood vessels to dilate. As part of this feedback loop, baroreceptor activity inhibits ongoing activity in the LC. Previous intervention studies have found that regular sessions of resonance frequency breathing over the course of several weeks can reduce blood pressure and improve baroreflex sensitivity. In the proposed study, we examine whether the practice can also shift LC activity to a less tonic, more phasic, pattern. In our 10-week intervention, we will randomize participants to either resonance-paced breathing or to a control breathing condition. We will have participants do a task (both before and after the intervention) in which LC function is associated with tau pathology. The task requires subjects to match faces to names. In this task, older adults exhibiting larger phasic responses to novel face-name pairs show less tau pathology in the entorhinal cortex, one of the first places tau tangles emerge when brainstem tau spreads to the cortex. We predict that the daily resonance frequency breathing will downregulate tonic LC activity... ## Key facts - **NIH application ID:** 10991245 - **Project number:** 3R01AG080652-02S1 - **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA - **Principal Investigator:** MARA MATHER - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $308,754 - **Award type:** 3 - **Project period:** 2023-01-15 → 2027-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10991245 ## Citation > US National Institutes of Health, RePORTER application 10991245, Effects of Resonance-Frequency Breathing on Preclinical Alzheimer’s Disease Biomarkers and Cognition (3R01AG080652-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10991245. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*