# Pathological and cognitive correlations of real time quaking induced conversion in LBD and AD

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $167,631

## Abstract

Project Summary/Abstract
 The accurate clinical diagnosis of Lewy body diseases (LBD: Parkinson’s disease (PD), dementia with Lewy
bodies (DLB)), and Alzheimer’s disease (AD) is challenged by overlapping clinical features. Novel biofluid
biomarkers including real time quaking induced conversion (RT-QuIC) offer the ability to diagnose patients with
greater accuracy during life by identifying pathologic α-synuclein (a-syn) or tau seeds. However, in LBD,
approximately 50% of cases will harbor significant AD pathology, and in AD up to 50% harbor limbic a-syn which
can complicate interpretation of biomarker signatures. Therefore, comprehensive pathological validation studies
are essential to understand the utility of these new assays and their association with histopathologic burden and
clinical correlations. If RT-QuIC metrics relate to pathological burden or cognitive outcomes, they could be used
as an objective biomarker in LBD, an ongoing critical need. The aims of this proposal are to test whether a-syn
and tau RT-QuIC is associated with 1) histopathological features and 2) cognitive outcomes in LBD and AD. The
hypotheses are that a-syn and tau RT-QuIC will be able to predict primary and co-pathologies in LBD and AD
and that higher degrees of RT-QuIC activity will associate with greater neuropathological burden and worse
cognitive outcomes. The proposed experiments will leverage pre-existing autopsy cohorts with antemortem CSF
and cognitive testing collected at the University of California San Diego (UCSD) and the University of
Pennsylvania with the RT-QuIC expertise of the NIH/NIAID Rocky Mountain Laboratories.
 The K23 candidate is an Assistant Professor of Neurosciences at the UCSD, having previously completed
movement disorders fellowship and a NIH TL1-supported Masters of Translational Research. He has a history
of productivity, having conducted translational and clinical research in neuroscience, recently focusing on the
neuropathology of PD, DLB, and AD. The candidate is committed to a career in translational research and
proposes a comprehensive five year plan of mentorship, formal training, self-directed learning, and research.
This K23 career development award will support Dr. Coughlin’s short-term goals, including 1) developing a
detailed understanding of RT-QuIC and its association with histopathological and cognitive outcomes, 2)
acquisition of skills for multimodal tissue characterization using immunohistochemistry and Western blotting
techniques, 3) learning the neuropsychology of dementia with a focus on LBD and AD, and 4) learning the
statistical methods to carry out these and future studies. Dr. Coughlin will meet these objectives under the
guidance of a mentorship team, including Dr. Douglas Galasko, an expert in biofluid biomarkers, Dr. Robert
Rissman PhD, an expert in the molecular pathology of neurodegenerative disease and Dr. David Salmon PhD
expert neuropsychologist with a long research track record in LBD and AD. This awa...

## Key facts

- **NIH application ID:** 10302212
- **Project number:** 1K23NS120038-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** David G Coughlin
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $167,631
- **Award type:** 1
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302212

## Citation

> US National Institutes of Health, RePORTER application 10302212, Pathological and cognitive correlations of real time quaking induced conversion in LBD and AD (1K23NS120038-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10302212. Licensed CC0.

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