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

Martin, Ryan (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/tb09j655b?locale=es
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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

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