The Vossel Lab studies molecular mechanisms of tau through techniques including proximity ligation assay, live cell signaling assays, slice electrophysiology, and electroencephalography. These assays allow us to see which molecules of interest the tau protein interacts with and provides a detailed picture of the synaptic integrity and plasticity within brain regions of interest.
Dr. Vossel’s clinical studies with Alzheimer’s disease patients revealed that over 40% of patients exhibit silent epileptiform activity, occuring during sleep, and this subclinical phenomenon could accelerate disease progression. Additionally, up to 20% of Alzheimer's patients develop seizures and associated cognitive decline. Therefore, up to 60% of Alzheimer's patients have seizures and epileptiform activity and could benefit from anti-seizure treatments. The Vossel lab has also demonstrated that patients with dementia with Lewy bodies have increased risk of seizures and myoclonus, which can hasten cognitive decline. To further understand seizure/epileptiform activity’s contribution to network dysfunction in dementia, the Vossel Lab uses electroencephalography (EEG) recordings in mice treated with antiseizure drugs or tau modifications. Studies using EEG recordings in models of neurodegenerative disease provide valuable insight into assessing how the blockade of certain biological processes may ameliorate overall network dysfunction.
Frontotemporal dementia (FTD) rarely occurs in individuals under the age of 30, and genetic causes of early-onset FTD are largely unknown. Our labrecently discovered retrotransposition of the MATR3 gene, a DNA/RNA binding protein, associated with early-onset FTD. This is a novel mutation mechanism of MATR3, although other mutations in MATR3 has been associated with FTD/ALS pathology previously. Retrotransposons are not often implicated in neurodegenerative diseases; thus, the Vossel lab is clarifying the potential role of MATR3 retrotransposition in early-onset FTD.