Roles for cell-cell signaling in the spread of Aβ42-mediated pathology in Drosophila eye model

Title

Roles for cell-cell signaling in the spread of Aβ42-mediated pathology in Drosophila eye model

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Description

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder with no cure and few effective treatments. AD causes profound cognitive deficits and memory impairments. Here we use a Drosophila model of AD to study the interactions between diseased and healthy cells to better understand the spread of the disease through the brain. Accumulation of the peptide amyloid beta into plaques is one of the characteristics of the disease. A 42 amino acid peptide, Aβ42, is a cleavage product of Amyloid Precursor Protein. Aβ42 tends to aggregate and forms oligomers, eventually making up the plaques seen in the disease. Human Aβ42 can be expressed in the developing retinal cells of fruit flies. In this study we use twin-spot MARCM (Mosaic Analysis with a Repressible Cell Marker) with the FLP/FRT system to express Aβ42. This yields animals with GFP-negative WT cells adjacent to GFP-positive Aβ42-expressing cells in a heterozygous background. We found that populations of Aβ42-expressing cells are much larger than the adjacent populations of WT cells. This suggests that cell-cell signaling between the two populations may be either interfering with the proliferation of WT cells or inducing cell death at a later stage in development. Previous research has implicated Aβ42 in the aberrant activation of pathways leading to cell death. Here we present evidence that signaling between Aβ42-expressing cells and adjacent WT cells mediates neurodegeneration.

Publication Date

4-24-2019

Project Designation

Independent Research

Primary Advisor

Madhuri Kango-Singh, Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium poster

Comments

Presenters: Prajakta D Deshpande, Catherine Jean Yeates

Roles for cell-cell signaling in the spread of Aβ42-mediated pathology in Drosophila eye model

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