Targeting Brain Cell Miscommunication to Restore Memory in Alzheimer’s Disease

Identify and therapeutically target activity-dependent transcriptomic and molecular signatures underlying disrupted interneuron/astrocyte communication, which contributes to synaptic dysfunction.

The brain’s ability to adapt and change, known as synaptic plasticity, requires the expression of specific genes and proteins in different brain cells, neurons and astrocytes, which is affected in brain disorders like Alzheimer’s. In order to find potential therapeutic strategies to recover synaptic plasticity, cell communication, and to improve memory in Alzheimer’s, we will use advanced techniques in mouse models and lab-grown human cells with Alzheimer’s-like pathology. Our results will contribute to the development of improved treatments for patients with synaptic plasticity disorders.

This proposal uniquely combines synaptic plasticity stimulation with advanced transcriptomics in tauopathy, enabling us to identify activity-dependent, cell-type-specific gene expression changes crucial for understanding synaptic dysfunction in neurodegenerative diseases (ND). This approach goes beyond static gene expression analysis and provides a dynamic view of the transcriptome in the context of synaptic activity. It has the potential to revolutionize our understanding of the molecular mechanisms underlying memory loss in ND and accelerate the development of more effective treatments.

Successful completion of this project may reveal new therapeutic targets for Alzheimer’s disease and related dementias (ADRD), especially those related to astrocyte and interneuron function. This study will provide a deeper understanding of the cellular and molecular mechanisms underlying synaptic dysfunction in ADRD, focusing on the role of astrocytes and interneurons communication in modulating synaptic plasticity and gene expression. This knowledge could potentially lead to the development of more effective, targeted treatments that may slow or even reverse cognitive decline in ADRD.