2025 Undergraduate Research Showcase

Document Type

Student Presentation

Presentation Date

4-15-2025

Faculty Sponsor

Dr. Troy Rohn

Abstract

Alzheimer’s disease (AD) is a progressive, fatal neurodegenerative disorder, and the most common cause of dementia. In addition to advancing age, there are known genetic risk factors associated with AD. Of the genetic risk factors identified, the 34 kDa protein apolipoprotein (Apo) E4 is significant, as ApoE4 carriers account for 65-80% of all AD cases. Recent data from the Rohn lab suggests that a 151 amino-terminal fragment of ApoE4 (nApoE41-151) can traffic to the nucleus, leading to toxicity and expression of inflammatory genes. We developed a stable zebrafish line through Tol2 transgenesis by creating a fusion construct that links the ApoE41–151 fragment with a self-cleaving 2A peptide and mCherry reporter. F2 homozygous mutants showed standard cardiac expression of the reporter and fragment, but about 10% of them also showed a significant loss of pigmentation, paralleling albinism. Quantitative image analysis demonstrated that pigmented area measurements in mutants were substantially lower than those in wild-type controls (p = 0.03) and approached the levels of true albino zebrafish (p = 0.039). We hypothesize that ApoE41–151 disrupts pigment cell development through interference with bone morphogenetic protein (BMP) signaling, which is vital for neural crest-derived melanophore differentiation. Zebrafish serve as a valuable research model to study systemic effects of Alzheimer’s-related genetic risk factors, and demonstrate that ApoE4 neurotoxicity can cause disrupted pigmentation.

Comments

This study was funded by the NIH Blueprint for Neuroscience Research 2R15AG042781-03 to Troy T. Rohn. The project described was also supported by Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grants #P20GM103408 and #P20GM109095, Directorate for Biological Sciences, 0619793, 0923535 to Julia T. Oxford.

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