# Combining electron and nuclear magnetic resonance to track Alzheimer's amyloid-beta oligomer-to-fibril conversion

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $238,776

## Abstract

Project Summary/Abstract
 Aggregation of Aβ protein plays a central role in the pathogenesis of Alzheimer's disease. Aβ aggregation
leads to the formation of soluble oligomers and insoluble fibrils. While amyloid fibrils are the main component
of parenchymal plaques in Alzheimer's disease brains, the Aβ oligomers have been widely regarded as more
toxic and more pathologically relevant. There is strong evidence supporting that at least some types of Aβ
oligomers can undergo a conformational conversion to form fibrils. It is yet poorly understood how the
oligomers could re-arrange their structures to form fibrils. In this proposed project, we will use a combination of
electron and nuclear magnetic resonance to monitor structural changes during Aβ42 oligomer-to-fibril
conversion. The Aβ42 oligomers will be prepared in the presence of low concentrations of detergent. These
Aβ42 oligomers represent a type of stable oligomers, which convert to fibrils only in the presence of lipid
vesicles. The oligomer-to-fibril conversion will be followed by performing EPR and NMR experiments at
different time points. This study will provide insights into whether oligomers dissociate to monomers, which
then nucleate to form fibril nuclei, or oligomers transition to the structure of fibril nuclei without dissociation. We
will not only delineate the mechanism of Aβ aggregation, but also shed light on how to modulate this process
as a way of therapeutic intervention.

## Key facts

- **NIH application ID:** 10662904
- **Project number:** 1R21AG082041-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Zhefeng Guo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $238,776
- **Award type:** 1
- **Project period:** 2023-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10662904

## Citation

> US National Institutes of Health, RePORTER application 10662904, Combining electron and nuclear magnetic resonance to track Alzheimer's amyloid-beta oligomer-to-fibril conversion (1R21AG082041-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10662904. Licensed CC0.

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