Physiological Method for Early Detection of Synaptic Vulnerability in Alzheimer’s Disease Model Animals



Alzheimer’s disease is the third most common disease affecting the U.S. population. AD is an age‐dependent chronic neurodegenerative disease, characterized by the accumulation of protein plaques in the brain, and loss of memory and cognitive capacity. Prior to the detection of brain plaques and behavioral changes, synaptic dysfunction begins to emerge and appears to lead to cognitive deterioration in AD patients in a vicious downward cycle. Hence, AD is recognized as a disease of synaptic failure. This project seeks to develop an optical imaging method for detecting early changes in synaptic function occurring in animal models of Alzheimer’s disease.


Multiple factors will cause or contribute to synaptic dysfunction in Alzheimer’s disease. The excessive production or accumulation of amyloid beta peptide has been documented to have deleterious effects on synaptic activity by various mechanisms. Many scaffolding proteins like mGluR proteins, Shank, Homer and postsynaptic density 95 are known to form complexes at synaptic terminals, and amyloid beta accumulation at synaptic terminals leads to disruption of these scaffolding protein interactions. Synaptic changes occur prior to the detection of brain plaques and behavioral changes associated with cognitive deterioration in Alzheimer’s disease. Alzheimer’s disease is recognized as a disease of synaptic failure. This project proposes the development of an optical imaging method for detection of early changes in synaptic function occurring in animal models of Alzheimer’s disease.

Funding to Date



Biomarkers/Diagnostics/Studies of Risk & Resilience, Foundational


Riqiang Yan, Ph.D

Srdjan D. Antic, M.D.

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