# Molecular mechanisms of membrane disruption induced by early-stage aggregation of beta-amyloid peptides

> **NIH NIH R01** · STATE UNIVERSITY OF NY,BINGHAMTON · 2021 · $274,818

## Abstract

Project Summary
 Because of the recent failures in the development of anti-amyloid therapeutic strategies for curing
Alzheimer's disease (AD), it is prompt to re-evaluate the existing amyloid cascade hypothesis from all possible
aspects. Among all these efforts, biophysical and structural characterizations of β-amyloid aggregates in in-
vitro model systems, especially the works that involve the high-resolution solid-state nuclear magnetic
resonance (ssNMR) spectroscopy, provide invaluable information from the fundamental sides. However so far,
most of these high-resolution works have been focused on the atomic structures of either amyloid fibrils or non-
fibrillar aggregates. Very little high-resolution studies have been performed to directly probe the cellular
membrane disruption effects induced by the aggregation process of β-amyloid peptides, which are potentially
associated with the neurotoxicity mechanisms of the β-amyloid aggregates.
 A major challenge that prevented the high-resolution studies of β-amyloid-peptide-induced membrane
disruption effects in model systems was the heterogeneity, which usually involved co-existence of multiple
membrane disruption pathways with mixed intermediate structures. This proposal attempts to solve this
problem by generating model systems with distinct predominant membrane disruption effects. These model
systems, which contain different β amyloid aggregates and phospholipid liposomes, are characterized by
distinct time-dependent membrane disruption features and structurally homogeneous endpoints. Therefore,
they can be studied individually in terms of their membrane disruption effects using high-resolution ssNMR
approaches.
 The outcomes of this proposal, if successful, will provide crucial insights on the high-resolution
molecular interactions between β amyloid aggregates and membranes that are responsible to the membrane
disruption. These information help to explain the neuronal cellular toxicity of β-amyloid aggregates, which
further contribute to the re-evaluation of amyloid cascade hypothesis.

## Key facts

- **NIH application ID:** 10073520
- **Project number:** 5R01GM125853-04
- **Recipient organization:** STATE UNIVERSITY OF NY,BINGHAMTON
- **Principal Investigator:** Wei Qiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $274,818
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073520

## Citation

> US National Institutes of Health, RePORTER application 10073520, Molecular mechanisms of membrane disruption induced by early-stage aggregation of beta-amyloid peptides (5R01GM125853-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073520. Licensed CC0.

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