# Investigating the role of neuroinflammation in Limbic-predominant age related TDP43 encephalopathy

> **NIH NIH K08** · NORTHWESTERN UNIVERSITY · 2020 · $163,251

## Abstract

PROJECT SUMMARY
This NIH Career Development Award proposal describes a five-year career development and training plan for
Dr. Margaret Flanagan, a physician-scientist in the Division of Neuropathology in the Department of Laboratory
Medicine and Pathology at the University of Minnesota. Her long-term goal is to become an independent,
physician-scientist leader who will make significant contributions in the field of dementia research. Her career
development training plan includes the following: protected research time, focused formal graduate coursework
targeted to advance her knowledge and skills in Epidemiology, a structured mentoring program with a
multidisciplinary team of experienced senior scientists, and focused research experience investigating the role
of neuroinflammation in Limbic predominant age-related TDP43 encephalopathy (LATE). This training plan
will culminate in a successful application for independent research funding by an investigator who is prepared
to take an active leadership role in transformative change leading to improved health care outcomes in
dementias associated with transactive response binding protein-43 (TDP43) associated inflammation, including
Alzheimer Disease (AD), hippocampal sclerosis of aging and frontotemporal dementia.
TDP43 is a highly conserved nuclear riboprotein that plays a role in a variety of cellular functions including
RNA processing. More recently, it has been shown that age-related increases in dementia risk are attributed to
the accumulation of multiple co-existing brain lesions, each of which contributes significantly to dementia risk.
Because there are no reliable biomarkers for TDP43 or α-synuclein, it is currently impossible to accurately
detect all co-existing lesions in vivo, limiting these comprehensive assessments to postmortem studies of the
brain.
The objective of this proposed research is to clarify the role of neuroinflammation in LATE clinical disease
progression. Dr. Flanagan will investigate TDP43 associated inflammatory markers relevant to pathways of
interest, co-existing neuropathologic lesions, LATE genetic risk variants and cognitive performance data in
well-characterized samples from Mayo Clinic. This work will inform on the role of TDP43-associated
neuroinflammation in the development of cognitive impairment and dementia in late life and ultimately, enable
the development of future preventative and therapeutic interventions. This research will provide some of the
first information about neuroinflammation in LATE.
In summary, a comprehensive career development plan in the context of a well-defined training, research and
mentorship structure will allow Dr. Flanagan to become a successful, independent physician-scientist.

## Key facts

- **NIH application ID:** 9870080
- **Project number:** 1K08AG065463-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Margaret E Flanagan
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $163,251
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870080

## Citation

> US National Institutes of Health, RePORTER application 9870080, Investigating the role of neuroinflammation in Limbic-predominant age related TDP43 encephalopathy (1K08AG065463-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9870080. Licensed CC0.

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