# Examining Amyloid-β Structure During the Progression of Alzheimer’s Disease using an Immuno-2DIR-Sensor

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $187,150

## Abstract

Examining Amyloid-β Structure During the Progression of Alzheimer's Disease using an Immuno-2DIR-
Sensor
Abstract
Alzheimer's disease is estimated to affect 30 million people and is the most common cause of dementia. It is
known that the disease is associated with plaques formed by Aβ aggregating into long β-sheet-rich fibrils. The
disease progression is probably associated with the formation of Aβ oligomers that are toxic to neurons.
However, obtaining structural information about these oligomers is exceedingly difficult, because they reside in
very small concentrations in the body. The purpose of this proposal is to develop an assay that can monitor the
structural distributions of Aβ extracted from serum and cerebrospinal fluid of healthy and Alzheimer's inflicted
individuals. The proposal is made possible by a new breakthrough in the sensitivity of 2D IR spectroscopy,
enabling data collection on a single monolayer of proteins. This new capability allows us to measure the 2D IR
spectra of Aβ polypeptides that are extracted from blood using antibodies in a flow-through sample cell.
Indeed, our approach is derived from very exciting ATR-FTIR reports that recently found that the amide I
frequency of Aβ is correlated to the progression of the disease, which indicates that the distribution of
structures of Aβ evolves as the disease progresses. The proposed 2D IR assay will be more sensitive and
provide more structural insight than the original ATR-FTIR work. Aim 1 of this proposal is to develop the 2D IR
version of the assay and use it to measure in vitro generated monomers, oilgomers, and fibrils of Aβ
polypeptides. These experiments will give insight into the biophysical mechanism of Aβ aggregation, especially
low population species that can play outsized roles in the nucleation of Aβ fibers, as well as generate a library
of reference 2D IR spectra. Aim 2 will be to use the assay to extract Aβ from blood plasma and cerebral spinal
fluid to monitor the structure of Aβ with the progression of the disease. Samples will be provided by the
Wisconsin Alzheimer's Disease Research Center. The libraries from Aim 1 will help parse the structural
distributions. This proposal is high risk because it utilizes a brand new technology, but also has the potential for
high impact, since the structural insights that promise to be gained on in vivo Aβ would be difficult, if not
impossible, to obtain any other way.

## Key facts

- **NIH application ID:** 9856395
- **Project number:** 5R21AG061602-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Martin T Zanni
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $187,150
- **Award type:** 5
- **Project period:** 2019-02-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856395

## Citation

> US National Institutes of Health, RePORTER application 9856395, Examining Amyloid-β Structure During the Progression of Alzheimer’s Disease using an Immuno-2DIR-Sensor (5R21AG061602-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9856395. Licensed CC0.

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