Date of Award


Degree Type

Honors College Thesis

Academic Program

Chemistry BS


Chemistry and Biochemistry

First Advisor

Vijay Rangachari, Ph.D.

Second Advisor

Bernd Schroeder, Ph.D.

Third Advisor

Sabine Heinhorst, Ph.D.

Advisor Department

Chemistry and Biochemistry


Alzheimer disease (AD) is a neurodegenerative disorder that leads to memory impairment and cognitive dysfunction in elderly populations worldwide. A key characteristic of AD is the formation of neuritic plaques composed of extracellularly deposited aggregates of amyloid-β (Aβ), an intrinsically disordered protein. Although Aβ fibrils were once thought to be the prime initiators of the disease, research has since been shifted to consider soluble, low molecular weight Aβ oligomers as the driving force behind AD toxicity. Due to its origin as a cleavage product of amyloid precursor protein (APP), an integral membrane protein, Aβ is known to perpetually interact with a variety of membrane lipids. We have previously characterized oligomerization of Aβ42 with lipid and fatty acids as well as GM1 ganglioside, an abundant component of membrane lipid rafts. These oligomers, coined GM1Os, exhibit unique biochemical and biophysical properties. Additionally, low levels of neurotransmitters such as acetylcholine (ACh) and dihydroxyphenylacetaldehyde (DOPAL) have been implicated in the onset of AD. This project involves the characterization of GM3- and GD3- bound Aβ42, which exhibits distinct properties, conformation, and effects on Aβ aggregation. Similarly, ACh and DOPAL were found to inhibit the aggregation of Aβ, confirming correlation between low levels of neurotransmitters and plaque formation. These findings suggest that different neuronal gangliosides interact differently with Aβ, which has implications on the varying degrees of toxicity in clinical AD pathology.

Keywords: amyloid-beta, protein aggregation, Alzheimer diseas, Oligomers, lipids

Included in

Biochemistry Commons