# Waters Select Series Cyclic IMS for P41 Native MS Resource Application to Alzheimer's Disease

> **NIH NIH P41** · OHIO STATE UNIVERSITY · 2020 · $250,000

## Abstract

Abstract.
The OSU NIH-funded P41 Resource “Native Mass Spectrometry Guided Structural Biology” proposes to develop
native mass spectrometry (nMS) -based tools for the characterization of protease-resistant protein
aggregates/oligomers associated with Alzheimer’s disease and its related dementias (AD/ADRD). The Resource
students, postdocs, faculty, and staff have no prior Alzheimer’s disease expertise or funding so this supplemental
funding would engage multiple new investigators in AD research, carry the expertise forward as students and
postdocs move on to other locations, disseminate the results, and provide a community resource to AD
investigators, and their MS core facilities at their local units. The nMS-based tools that currently exist in the P41
and tools under development will be used to tackle the AD problem (nMS coupled to ion mobility and multiple
activation methods (surface-induced dissociation, collision-induced dissociation, electron capture dissociation)
and covalent labeling methods if needed). In order to study AD related aggregates and oligomers, this
supplement proposes purchase of a production model Waters Select Series Cyclic IMS instrument,
which will be modified by the Resource to include surface-induced dissociation. The proposed instrument
is more sensitive and has higher m/z and ion mobility (IM) resolution than the 8-year-old Waters Synapt Series
instruments currently in the Resource. The one-year supplement term will focus on method development on the
Cyclic IMS for samples from the Nowick lab at UC Irvine (amyloid beta oligomers and amyloid oligomer mimics)
and the Kuret lab at OSU (tau). Additional samples, including brain tissue and antibodies and other probes under
development, will be provided by Nowick, Kuret, and collaborators of Kuret who are planning to jointly apply for
U24 funding. The Resource will work with investigators to illustrate the complementarity of native MS with other
structural biology tools, based on experience developed in ongoing non-AD Driving Biomedical Projects and
Collaboration & Service projects. At the end of this development, additional AD investigators will be encouraged
to propose to work with the P41 under its Collaborate and Service, Training, and Dissemination missions, to
work with one of the external core facilities that have been trained in nMS approaches for AD investigations, or,
eventually, to work with the OSU U24 Resource network, if funded. Specific Aims are to develop nMS/IM/MS
tools for i) in vitro tau and Aβ oligomers and Aβ oligomer mimics, ii) in vitro chemical or molecular probes binding
to -oligomers, and iii) aggregates/oligomers and probe-bound oligomers from brain tissue. Developing robust
and reliable methods for understanding how both Aβ and tau aggregate in vitro is essential to better understand
the molecular mechanism of AD, and consequently for developing effective diagnostic tools and therapies.
Characterization of probe/oligomer interactions and assessin...

## Key facts

- **NIH application ID:** 10123851
- **Project number:** 3P41GM128577-03S1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Vicki H. Wysocki
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123851

## Citation

> US National Institutes of Health, RePORTER application 10123851, Waters Select Series Cyclic IMS for P41 Native MS Resource Application to Alzheimer's Disease (3P41GM128577-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10123851. Licensed CC0.

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