Alzheimer’s Disease Pathophysiology Alters the Level of Electrical and Chemical Synapse Coupling in the Network of GABAergic PV+ Interneurons Early in Disease Course


Alzheimer’s disease (AD) is an age-dependent chronic neurodegenerative disease, characterized by accumulation of aberrant proteins in the brain (amyloid beta and tau), loss of memory and cognitive capacity. At early stages of disease, prior to the detection of brain plaques and significant behavioral changes, a dysfunctional neuronal activity begins to emerge, and it appears that this neuronal electrical activity promotes faster degeneration of the brain tissue, leading to irreversible cognitive deterioration. A vicious downward cycle thus may exist: initially, the AD-mediated production of toxic materials (amyloid beta and tau) triggers stronger neuronal activity in some parts of the brain circuit, and then this aberrant neuronal activity accelerates the production of the same toxic materials (amyloid beta and tau). This project seeks to determine the components of the neural circuit that are sensitive to increased levels of amyloid beta and tau in animal models of AD. We are especially keen to investigate early stages of AD, before a significant accumulation of protein plaques inflicts irreparable damage to the brain structures. Once we identify the vulnerabilities in the brain circuit, we might then be able to develop therapeutic approaches to protect these neural circuits from the ongoing AD pathology.

Funding to Date



Studies of Alternative Neurodegenerative Pathways, Translational


Srdjan D. Antic, M.D.

Riqiang Yan, Ph.D