Jennifer Villwock, MD, Awarded Funding for Novel Alzheimer’s Biomarker Research

Innovations in Ear, Nose & Throat | Summer 2026

Jennifer Villwock, MD, and her multi-institutional collaborators recently received more than $57,000 to investigate the link between mitochondrial dysfunction and Alzheimer's disease (AD) in mouse models.

Jennifer Villwock, MD

Dr. Villwock is Vice Chair of Research in the Department of Otolaryngology – Head and Neck Surgery and a fellowship-trained rhinologist and anterior skull-base surgeon at University Hospitals, and Professor of Otolaryngology at Case Western Reserve University School of Medicine. Her research focuses on understanding olfactory phenotypes – or patterns of performance on sense of smell tests – exhibited by patients with and without other health conditions.

“While we know that decreased sense of smell is linked to Alzheimer’s disease and our data is showing a similar association with plasma biomarkers, we don’t know why this occurs,” Dr. Villwock says. “Understanding the ‘why’ is critical to developing novel therapies and treatment approaches. With this additional funding, we hope to better understand the science behind changes in the olfactory system — especially in the olfactory epithelium and the olfactory sensory neurons — that may contribute to the early development and progression of Alzheimer’s disease and related dementias.”

The team received $7,325 through the Clinical and Translational Science Collaborative Voucher Award, which is funded by the National Institutes of Health (NIH), National Center for Advancing Translational Sciences, Clinical and Translational Science Award grant.¹

The team was also among the six selected from 44 applicants to receive $50,000 through the 2026 Case Western Reserve University and University Hospitals Collaborative Science Pilot Award.

Working with Dr. Villwock in Cleveland are:

• C. Ron Yu, PhD, Chair of the Department of Neurosciences at the School of Medicine, an expert with the only available mouse model of olfactory dysfunction.
• Ruben Stepanyan, PhD, Associate Professor of Otolaryngology – Head and Neck Surgery at the University Hospitals Ear, Nose & Throat Institute, an expert in hearing loss who is developing expertise in analyzing mitochondrial function.

The team is also collaborating with world-renowned experts, including:

• Artur Indzhykulian, MD, PhD, an Investigator in the Eaton-Peabody Laboratories at Mass Eye and Ear/Harvard Medical School, using state-of-the-art optical and electron microscopy techniques.
• Mark Albers, MD, PhD, a Neurologist specializing in memory and olfactory disorders at Mass General/Harvard Medical School.

“Research like this requires longstanding connections within the scientific community at leading academic medical centers,” Dr. Villwock says. “For example, dissecting the olfactory sensory neurons and associated epithelia and then using sophisticated electron microscopy techniques is a highly specialized field that does not happen in isolation. We are excited to continue combining our expertise in this logical extension of the work we are already doing, with the hope of achieving the highest impact.”

AD and related dementias affect millions worldwide, yet their underlying causes remain poorly understood. Current treatments targeting amyloid plaques show only modest clinical benefits, underscoring the need to investigate other disease mechanisms.

“Why does Alzheimer's disease happen?” Dr. Villwock asks. “There are several different hypotheses, and it’s likely that multiple are contributing to the development of Alzheimer’s disease. For example, the protein hypothesis is most well-known and posits that abnormal amyloid and tau proteins accumulate in the brain and cause problems. There is also the mitochondrial dysfunction hypothesis, which is what we are focusing on. This theorizes that changes in mitochondrial function lead to problems in the ability to generate energy and carry out processes required for cellular functioning, which might start — or contribute to — the cascade of events that lead to an abnormal collection of dysfunctional proteins or inflammation seen in Alzheimer’s disease.”

The team’s findings could help identify early biomarkers for minimally invasive diagnosis and support the development of new intranasal therapies that target mitochondrial dysfunction, potentially transforming how dementia is detected and treated.

“What is exciting from my perspective is that the olfactory sensory neurons are a relatively easily accessible target for therapeutics,” Dr. Villwock says. “Medication in the form of a nasal spray could be delivered in a relatively noninvasive way to potentially help restore mitochondrial function. That goal is obviously many steps away, but hopefully we will reach the point where that is a possibility.”

Next steps include expanding mouse models, staining cells to assess inflammation and other markers of cellular health, conducting detailed immunofluorescence analysis, and performing focused ion beam scanning electronic microscopy. As the team works through the research phases funded by their current funding, they are also preparing an NIH R01 application for submission this fall.

¹ UM1TR004528.