# Investigating structural heterogeneities in amyloid aggregates with multiscale infrared spectroscopic imaging

> **NIH NIH R35** · UNIVERSITY OF ALABAMA IN TUSCALOOSA · 2023 · $360,271

## Abstract

Project Summary
The misfolding and aggregation of specific proteins into fibrillar amyloid deposits is the pathological hallmark of
a wide class of diseases and neurodegenerative disorders, which represent a major public health concern
worldwide. While it is recognized that amyloid aggregates play an active part in the molecular pathology of the
disease, the exact aggregation states that causes cytotoxicity and relationship between pathogenesis and the
distribution of secondary structures in amyloid aggregates is not well established. The aim of this project is to
investigate the heterogeneities in protein secondary structure in amyloid aggregates both in-vitro and ex-vivo
and identify their relationship with disease progression. Our approach relies on utilizing state-of-the-art
nanoscale infrared (IR) spectroscopy and confocal IR spectroscopic imaging to map protein secondary structures
in amyloid deposits. We will focus on studying amyloid aggregates and their heterogeneities in Alzheimer’s
disease (AD) to develop and optimize our methods, and subsequently aim to extend these strategies to
investigate amyloid aggregates in other diseases such as Parkinson’s disease and Breast Cancer. The
hypothesis underlying this effort is that structural heterogeneities of amyloid deposits, and not just specific fibrillar
structures, are correlated with disease progression. We will utilize photothermal AFM-IR, a technique that
augments IR spectroscopy with Atomic Force Microscopy, to obtain nanoscale aggregate-specific spectra.
Seeded growth from tissue extracts from AD patients will enable probing the differences in aggregation pathways
and structural polymorphisms associated with different disease stages. Amyloid aggregates in tissues will be
investigated through confocal IR microscopy. The tissue spectral data will be analyzed to classify amyloid
deposits based on their secondary structure distributions, and the correlation between distinct classes of deposits
and disease stages will be explored. We further aim to integrate AFM-IR and IR microscopy and develop a
spatially and spectrally adaptive IR imaging approach that will enable multiscale measurement of spectral data
in tissues. The unique aspect of this approach is that it uses cutting edge technologies in spatially resolved IR
spectroscopy and imaging to investigate a problem that is central to the molecular pathology of a wide range of
diseases and development of therapeutic strategies.

## Key facts

- **NIH application ID:** 10698086
- **Project number:** 5R35GM138162-04
- **Recipient organization:** UNIVERSITY OF ALABAMA IN TUSCALOOSA
- **Principal Investigator:** Ayanjeet Ghosh
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $360,271
- **Award type:** 5
- **Project period:** 2020-09-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10698086

## Citation

> US National Institutes of Health, RePORTER application 10698086, Investigating structural heterogeneities in amyloid aggregates with multiscale infrared spectroscopic imaging (5R35GM138162-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10698086. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*