APPKO mice exhibit dysphagia symptoms separate from whole body sarcopenia Open Access

Zhu, Carol (Spring 2021)

Permanent URL: https://etd.library.emory.edu/concern/etds/x059c835b?locale=en
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Abstract

As the global population of elderly individuals continues to increase, economic and healthcare systems are strained by their need for long term care. One prevalent disease that impacts this demographic is Alzheimer’s Disease, making up more than half of dementia case, defined as general symptoms of cognitive decline. In addition to the accumulation of ß-amyloid plaques and worsening cognitive decline, other common early symptoms of Alzheimer’s include body weight loss, sarcopenia (loss of muscle mass), and dysphagia (difficulty swallowing), used as early diagnostic tools. This paper utilizes an APPKO mouse model with an amyloid precursor protein double knockout to study the relationship between sarcopenia and dysphagia, measured through lick rate. We hypothesized that APPKO mice exhibit dysphagia which leads to sarcopenia and body weight loss. This would be determined by phenotypic analysis, measurement of muscle fiber cross sectional area, and behavioral analysis. Our findings indicate that APPKO mice exhibit decreased body weight, slower rate of growth, and decreased lick speeds, although food and water consumption remain within normal range. Additionally, APPKO mice exhibit decreased endurance, locomotor activity, and TA muscle fiber size. Our findings suggest that behavioral and muscular deficiencies are independent of nutrient intake despite reduced pharynx muscle size.

Table of Contents

Table of Contents

INDEX OF FIGURES ......................................................7

INTRODUCTION: .....................................................8

Elderly populations suffer from high rates of dementia: ...................................................8

Alzheimer’s Disease presents in a range of neurodegenerative, cognitive, and physiological symptoms .........9

Understanding age related muscular weakness (sarcopenia): ......................................................10

Amyloid protein precursor mutations in mice provide an applicable modeling scheme .................11

Experimental objective and hypothesis: ......................................................13

METHODOLOGY ............................................................................................................14

Experimental Mice ......................................................14

Food and water consumption.......................................................14

Dysphagia assays......................................................14

Rotarod experiments......................................................15

Muscle collection.......................................................15

Cryostat sectioning......................................................15

Immunofluorescence staining......................................................16

Data interpretation:......................................................16

Statistical Analysis:......................................................17

RESULTS........................................................18

Figure 1:........................................................18

Figure 2:........................................................20

Figure 3.........................................................22

Figure 4a.......................................................24

Figure 4b:......................................................25

Figure 5.........................................................26

Figure 6:........................................................27

Figure 7.........................................................28

DISCUSSION:...........................................................................................................30

Overall findings and implications:......................................................30

Body weight results:......................................................30

Dysphagia results:......................................................31

Food and water consumption results:......................................................31

Analysis of locomotor function findings......................................................32

Muscle histology analysis:......................................................33

Implications:......................................................33

SOURCES CITED:............................................................................................................35

SUPPLEMENTAL FIGURES......................................................42

Supplemental Figure 1......................................................42

Supplemental Figure 2:......................................................43

Supplemental Figure 3:......................................................43

Supplemental Figure 4: ......................................................44

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