Paula Desplats

About

Biography

I am a professor of Neurology in The Ohio State University College of Medicine. My scholarly work centers on understanding and targeting the molecular mechanisms that drive neurodegenerative pathologies, especially Parkinson’s disease (PD) and Alzheimer’s disease (AD), with particular emphasis on epigenetic and circadian mechanisms. I am focused on developing novel biomarkers for diagnosis as well as chronotherapies to reduce pathology and cognitive decay.

My current work focuses on liquid biopsy approaches using cell-free DNA (cfDNA) to detect brain-derived signals in blood. My team and I have established robust protocols and generated preliminary data demonstrating increased cfDNA levels in Lewy body dementias and disease-specific methylation patterns that may reflect neuronal loss. These findings position cfDNA epigenomics as a promising tool for real-time detection and staging of neurodegeneration.

In parallel, my research investigates the role of circadian dysfunction in AD and related disorders. Using multiomic approaches – including whole-genome bisulfite sequencing, ATAC-seq, RNA-seq and spatial transcriptomics – we have generated comprehensive maps of rhythmic gene regulation in healthy and diseased brains. Our studies revealed widespread disruption of circadian rhythms in gene expression, chromatin accessibility and DNA methylation in AD models.

After discovering severe disruptions in the rhythms of activity and brain transcription that contribute to pathology in APP mice, we evaluated whether circadian modulation via feeding timing could ameliorate AD phenotypes. We found that time-restricted access to food (TRF) improved sleep and rescued behavioral abnormalities in APP mice. Moreover, TRF modulated the expression and rhythmicity of hundreds of AD and neuroinflammation genes in the hippocampus, functionally associated with myelination, transmitter synthesis and storage, autophagy, cytokine remodeling and immune response. Notably, TRF improved pathology in APP mice, significantly reducing plaque burden, attenuating disease progression, increasing Aβ clearance and, importantly, rescuing cognitive function.

Motivated by the lack of disease-modifying therapies, I have built a translational research framework that bridges mechanistic discovery with biomarker development and therapeutic innovation.

Strategies that improve health by modulating the circadian clock are gaining momentum. Interventions leveraging the entraining power of the feed/fast cycle have shown metabolic improvement, increased longevity, and reduced inflammation in both animal and human studies. The results from our TRF intervention are outstanding and place circadian disruption at the center of neurodegeneration. They also open avenues for lifestyle interventions that modulate the circadian clock to slow the disease progression. These strategies may particularly benefit underserved populations disproportionately affected by AD, thus curtailing inequality and supporting inclusivity in healthcare.

We are already translating these exciting findings to the clinic. Our long-term goal is to develop interventions that modulate circadian function to slow the progression of neurodegenerative disorders. Funded by an R61 award from NIA, we are recruiting participants for TREAD: “Time Restricted Eating for Alzheimer’s Disease” (Clinical Trial # NCT06548191). This study is testing the feasibility and efficacy of prolonging nightly fasting among patients across the continuum from cognitive impairment to AD.

We are set to provide rigorous data and quantifiable output measures regarding metabolic indicators of glucose and lipid regulation, sleep, activity rhythms, epigenetic aging, biomarkers of AD pathology and cognitive function. This critical step toward bringing this non-pharmacological intervention into clinical practice represents a significant achievement of my laboratory’s translational work.

Credentials

Research