Identifying How Tau Impairs Nerve Cell Communication in Alzheimer’s Disease

Ottavio Arancio, MD, PhD
Columbia University (New York, NY)

Co-Principal Investigators

Russell Nicholls, PhD
Columbia University (New York, NY)
Year Awarded:
Grant Duration:
July 1, 2018 to June 30, 2022
Alzheimer's Disease
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Northeastern
Ottavio Arancio, MD, PhD

Tau-Induced Damage at Hippocampal Tripartite Synapses


The cognitive and behavioral symptoms that characterize Alzheimer’s disease (AD) are thought to result from impaired communication between neurons in the brain at connections called synapses. Toxic forms of a protein called tau play a central role in AD and other neurodegenerative conditions, and recent data show that tau can interfere with synapses in multiple ways. These observations greatly underscore efforts to treat AD by blocking the pathological actions of tau. The goal of this project is to better understand how tau interferes with synaptic function so that we can develop effective strategies to block the impairments it causes.


A combination of high tech electrophysiological and molecular biological techniques will permit the exploration of changes occurring both pre- and post-synaptically, as well as at the level of astrocytes that surround synapses following the elevation of tau protein.

About the Researcher

Dr. Ottavio Arancio received his PhD and MD degrees from the University of Pisa (Italy).   From 1981 to 1986, he took residency training in neurology at the University of Verona (Italy).  Dr. Arancio has held faculty appointments at Columbia University, NYU School of Medicine and at SUNY Health Science Center Brooklyn.  In 2004, he became a faculty member of the Department of Pathology and Cell Biology and The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University.  His honors include the G. Moruzzi Fellowship (Georgetown University), the Anna Villa Rusconi Foundation Prize (Italy), the INSERM Poste Vert Fellowship (France), the AHAF centennial Award (2007), the Zenith Award (2007), the Margaret Cahn Research Award (2008), and the Edward N. and Della L. Thome Memorial Foundation Award (2010). Over the last 20 years, he raised more than $30 million in grant funding and published more than 100-peer reviewed manuscripts. Dr Arancio is a cellular neurobiologist who has contributed to the characterization of the mechanisms of learning in both normal conditions and during neurodegenerative diseases.  During the last 10 years, he has pioneered the field of mechanisms of synaptic dysfunction in AD.  More recently he has established a shockwave exposure mouse model for the study of traumatic brain injury. Dr. Arancio’s laboratory has focused primarily on events triggered by oligomeric proteins including amyloid-beta and tau.  These studies have suggested new links between synaptic dysfunction and dementia, both for understanding the etiopathogenesis of AD and traumatic brain injury, and for developing therapies aiming to improve the cognitive symptoms. Dr. Arancio has been featured on   []

Personal Story

Discovering how nature works has been my biggest passion in life. Early on in my career, I became fascinated by the implications of the communication among cells in the brain. Memories of facts, figures, faces and numbers are thought to be stored as changes in the strength of the signaling mechanisms among nerve cells in the brain. Considering that I always wanted to translate basic knowledge into a means to understand disease mechanisms, it became natural to me to work in Alzheimer's disease when I started my own laboratory after my post-doctoral years in the lab of Nobel laureate Eric Kandel, a worldwide known expert in the memory field. Since then, I have investigated faltering cell communication in the presence of proteins that are known to be involved in the disease. I am convinced that the individual connection between cells in the brain will provide the key to defeat this devastating disorder. Needless to say, I am really grateful to people that support our efforts and dedication to finding a therapy against the disease.

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