A Novel Approach for Memory Improvement in Alzheimer's Disease

Prof. Yingjun Zhao, PhD
Xiamen University (Fujian Sheng, China )

Collaborators

Robert Rissman, PhD
University of California San Diego (La Jolla, CA)
Year Awarded:
2018
Grant Duration:
July 1, 2018 to June 30, 2020
Disease:
Alzheimer's Disease
Award Amount:
$150,000
Grant Reference ID:
A2018214F
Award Type:
Postdoctoral Fellowship
Award Region:
International

This grant is made possible in part by the support of the J. T. Tai Foundation.

Yingjun Zhao, PhD

Targeting Synaptic and Memory Deficits in Alzheimer’s Disease

Summary

Note: The grant was transferred from Sanford Burnham Prebys Medical Discovery Institute to Xiamen University in March of 2019.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder worldwide and has devastating effects on memory and brain function in affected individuals. Although the exact causes that accelerate memory loss are not known, it is likely that a toxic protein amyloid beta (Aβ) plays a vital role in disrupting communication junctions in the brain as AD progresses.

Details

The major goal of this project is to characterize a novel mechanism for memory dysfunction in Alzheimer’s disease (AD). In Aim 1, we will determine how increasing or decreasing appoptosin expression levels can affect synaptic function through biochemical and high-resolution microscopy analysis. We will characterize changes in proteins required for synaptic function with the modulation of appoptosin expression levels in neurons, and quantify alterations in synaptic structures in these neurons. In Aim 2, we will determine whether reducing appoptosin levels can rescue synaptic and memory deficits in an AD mouse model. We will cross appoptosin knockout mice with Tg2576 AD lines and characterize synaptic activity, and memory formation/extinction in these mice through electrophysiological and behavioral analysis. We will also further characterize how reducing appoptosin levels can influence amyloid-beta (Aβ)-induced synaptic deficits in primary neuronal cultures. As appoptosin is a fundamental regulator of apoptosis and tau pathogenesis in AD, the key innovation of this project consists of exploring potential neuroprotective effects that may be associated with appoptosin downregulation. Moreover, our results implicate a novel role for appoptosin in memory formation/extinction; this implicates pleotropic neuroprotective effects through appoptosin modulation and attenuation of appoptosin function. Further, as previous studies in the AD field have focused exclusively on memory formation deficits, this may provide insight into memory extinction mechanisms that are dysregulated in AD. Successful completion of this study will help us understand how memory decay is regulated, and may bring insight into new therapeutic targets for AD. 

About the Researcher

Dr. Zhao is a postdoctoral associate at the Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute. He received his PhD degree in chemical biology from Xiamen University (Xiamen, China). His previous work focused on the intracellular trafficking of proteins associated with neurodegeneration, such as beta-secretase 1 and SNX27, and characterizing a novel role for the tauopathy risk gene appoptosin in tau pathogenesis. Currently, his major interest is to elucidate mechanisms underlying synaptic and cognitive deficits in Alzheimer’s disease (AD), and characterize the role of TREM2 (triggering receptor expressed on myeloid cells 2 variant) in microglia in the progression of AD. 

Personal Story

As the lifespan of the human population increases, the number of people suffering from aging-related diseases such as Alzheimer’s disease (AD) is slowly becoming a global problem. Unfortunately, this trend is compounded by the lack of a cure or treatment. Unless we make progress towards understanding and reversing the effects of this disease, this could potentially have devastating effects on the quality of life in countless individuals. I would like to thank BrightFocus Foundation and donors for providing the support for this project, which will help us gain new understanding of the manifestation of memory deficits in AD.

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