Lauren R. Mongeau¹, Lauren Bailey¹, Takeshi Murai¹, Abbey Setlik¹, Andrew DeSana¹, Afonso Silva², Stacey J. Sukoff Rizzo^1,2

¹Aging Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

²Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder and the most common form of dementia. While a primary symptom is cognitive decline, sensory deficits including impairments in taste and smell have emerged as early indicators of amyloid and tau pathology that precede cognitive impairment. The ability to discriminate the functional changes related to variation in normal healthy aging from those that lead to pathological aging, and the onset of AD may help predict the earliest accumulation of AD pathology and enable better detection, earlier diagnosis, and interventions for prevention and treatment. For these studies we leveraged a large population of marmosets including marmosets seeded with tau to evaluate the trajectory and progression of AD pathology and sensory and cognitive impairments.

Methods: Male and female marmosets across an age span ranging from 18 months to 16 years utilized for this task. Marmosets were initially habituated to the presentation of a panel fixed with two drinking bottles placed on the front of their homecages that both contained a 20% solution of marshmallow juice (MJ) formulated from dehydrated marshmallows into drinking water for a 10-minute session. Following the habituation session in which we verified that marmosets sampled from both bottles, we conducted a two-choice preference test in subsequent sessions with varying solutions of MJ (0.5%, 1%, 5%, 10%) or water, randomized for testing order and counterbalanced for side using a modified latin-square design. All 4 sessions were conducted on consecutive days of the week with a second week of testing presenting the same testing order but the opposite presentation for side from the previous week. The bottles were weighed before and after the session to determine the amount consumed and the preference ratio of the water to MJ. A dummy bottle was placed on the opposite side of the panel to account for potential leakage.

Results: Preference ratio was evaluated of animals that have tau pathology. All Marmosets could discriminate against the higher concentrations of 10% and 5% MJ relative to water. We saw differential responses at the 1% and 5%,

Conclusion: With this, we can establish typical marmoset taste discrimination longitudinally in wild-type marmosets, and marmosets with higher risk of tau pathology. Analysis of these studies provide characterization of gustation discrimination and decline in healthy marmosets and marmosets with risk of tau pathology across lifespan, which are being correlated with aging and AD related biomarkers to inform and predict cognitive decline associated with non-specific dementia.[LM1]

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• [LM1]Dementia progression (non-specific) impairs taste and smell (Waldton, 1974; Lang et al., 2006 Steinbach et al., 2010)