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Grants > Understanding Early Effects of Amyloid and Tau in Different Memory Domains Updated On: Feb. 2, 2025
Alzheimer's Disease Research Grant

Understanding Early Effects of Amyloid and Tau in Different Memory Domains

a headshot of Dr. Chen

Principal Investigator

Xi Chen, PhD

University of California, Berkeley

Berkeley, CA, USA

About the Research Project

Program

Alzheimer's Disease Research

Award Type

Postdoctoral Fellowship

Award Amount

$200,000

Active Dates

October 01, 2021 - September 30, 2023

Grant ID

A2021004F

Mentor(s)

William Jagust, MD, University of California, Berkeley

Goals

The goal of the project is to examine if the initial deposition of amyloid and tau may lead to certain memory deficits that reflect specific brain vulnerabilities in the related memory networks. The first aim of the project is to develop a new memory task that detects different types of memory deficits, by measuring memory for objects, scenes, and associations, separately. I will administer this task in older adults with and without amyloid and tau, and examine if having certain pathologies may be related to specific memory deficits. This task will be administered using fMRI, which records brain activity while participants complete the task. The second aim, thus, is to understand how amyloid and tau affect different regions in the brain that support different types of memory.

Summary

Beta-amyloid (Aß) and tau are two critical biomarkers of Alzheimer’s disease (AD). They start to deposit in the brain decades before the clinical symptoms of AD appear. Because there is no cure yet for AD, many research and clinical studies now emphasize the importance of the beginning stage of AD prior to the irreversible impairment. The proposed project, focusing on this early stage, will examine the brain and behavioral deficits in older adults with normal cognitive performance but already harboring AD pathology. This study will use functional MRI to investigate how different brain regions activate when participants view pictures of an object, a scene, and an object in a scene. Participants will complete a surprise memory test on the pictures 20 minutes later. By analyzing the pictures that they can remember in contrast to those that they cannot, I will be able to isolate brain activities that are critical for successful memory. Meanwhile, participants will also undergo PET imaging to visualize the deposition of Aß and tau in the brain. I will determine the specific effect of Aß and tau on different domains of memory performance (object, scene, and integrated object-scene memory) and what brain regions are most affected. This research will provide urgently needed information on specific memory deficits related to Aß and tau pathology and, in doing so, will help clinical research targeting specific pathologies to identify individuals optimal for certain therapeutic trials.

Unique and Innovative

This project innovatively proposes a new memory task that measures memory for object, scene, and their associations. Memory assessment in AD research has been almost exclusively on words and stories. This task uses common, everyday images, mimicking how memory works in real life. And its complexity makes it sensitive enough for detecting deficits even in the early stage of AD. The focus of specific links between pathology and memory function is also unique. It will provide crucial knowledge that could lead to better behavioral tests useful for early diagnosis and screening in clinical trials.

Foreseeable Benefits

The knowledge of specific links between amyloid/tau and certain memory deficits can help researchers develop new behavioral tests corresponding to a specific pathology, which could contribute to early diagnosis and screening for clinical research and therapeutic trials developing treatments targeting specific biomarkers. Currently, biomarker status can only be examined by conducting invasive or expensive procedures like a lumbar puncture or PET scan. Having sensitive and specific behavioral markers for certain AD pathology could also make large-scale screening for the general public possible.