Kiersten
Mackenzie Penquite

Coupled Risks of Lead Exposure and Genetic Variations in Alzheimer's Disease STEM

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Authors:

Kiersten Mackenzie Penquite

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Alzheimer's Disease makes up around 70% of dementia cases and results in faster cognitive decline. While the exact cause of AD is unknown, various genetic factors and environmental factors can increase an individual's risk of developing AD. One such environmental factor that has been linked to AD is lead exposure which was common around the 1970s when lead was commonly used in paint, soldering for water lines, and other industrial processes. However, it is not known how different genetic variations coupled with lead exposure affect the risk of AD development. Therefore, by utilizing CRISPR gene editing technology, a variety of genetic conditions can be introduced to induced neurons in a lab with lead exposure to study their combined effects on cell behavior. Data will be collected with CRISPR Droplet sequencing(CROP-seq) which will provide the transcriptome of each cell along with which gene has been edited. Additionally, cells will be grouped by expression of the protein tau which is found in high levels in AD patients. Based on the results of the CROP-seq it will be possible to determine which genetic conditions with lead exposure result in a similar pathology in the cultured neurons as is seen in native AD cases. By comparing transcriptome data and tau accumulation under lead exposure, it will be possible to identify gene-environment interactions that result in phenotypes like AD. Keywords: Alzheimer; CROP-seq; iPSCs; Tau Protein; Neurons

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Purdue University / 2025

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Co-authors:

Kiersten Mackenzie Penquite