Memory Assessment in a Nonhuman Primate Model of Alzheimer's Disease Using a Visual Paired-Comparison Task Open Access

Abstract

Importance: There is currently no animal model for Alzheimer's disease that fully recapitulates the etiologic, cognitive and pathological characteristics of the disease.

Objective: To determine if there is a transgenic nonhuman primate model of AD (AD monkey) recapitulates memory deficits present in human AD.

Measures: Visual Paired-Comparison task and quantitative PCR.

Subjects: The experimental group consists of two female AD monkeys aged between 9 and 10 years that contain the Swedish and Indiana mutations in βAPP under the control of human polyubiquitin promoter (APPswe/ind). Six macaques (3 males and 3 females) aged between 5 and 6 years were used as control. For molecular analysis, two female macaques aged between 9 and 10 years were used.

Results: Transgenic macaques displayed a significantly lower novelty preference on the Object-in-Place VPC task. All other differences in VPC tasks were not statistically significant. Up-regulation of the APP transcript in lymphocytes was observed in both AD monkeys. Down-regulation of ApoE, CX3CR1, and CXCL8 transcripts was observed in both AD monkeys.

Conclusion: AD monkeys show altered looking behavior on spatial-relational memory tasks, preferring familiar to novel stimuli. This altered looking behavior may be due to the increased expression of APP. A VPC task utilizing more visually similar stimuli than the VPC Color-Delay is required to determine if recognition memory is impaired.

Table of Contents

Introduction…………………………………………………………………………………….... 1

Methods……………………………………………………………….……………………....…..6

Figure 1: Stimuli present in VPC task variations…………….......……………...………13

Results……………………………………………………………………………...……………14

Figure 2: Color-Delay task…………………………………………...………………….18

Figure 3: Spatial-Location………....…………………………………………..………...19

Figure 4: Object-Replace………....……………………………...…………........……....20

Figure 5: Object-in-Place………....……………………….…………...……...………....21

Figure 6: Normalized RNA Lymphocyte Expression…………………......……………..22

Discussion……………………………………………………...………………………………...22

References………………………………………………………...……………………………...29

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Keyword	Monkey VPC eye-tracking Rhesus Task Macaque Memory Visual Alzheimer's
Committee Chair / Thesis Advisor	Chan, Anthony, Department of Human Genetics, Emory University School of Medicine, Division of Neuroscience
Committee Members	Walker, Lary C, Emory University Bachevalier, Jocelyne, Emory University Kazama, Andrew Masami, Emory University

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