# Role of Microglial Heterogeneity on Cognitive Resilience in Aging and Alzheimer’s Disease

> **NIH NIH K08** · MAYO CLINIC ROCHESTER · 2024 · $155,520

## Abstract

PROJECT DESCRIPTION/ABSTRACT
This NIH K08 proposal describes a five-year career development plan for Dr. Aivi T. Nguyen to obtain the
necessary research and professional skills and serve as transition to become a successful, independently
funded physician-scientist. Dr. Nguyen completed her clinical training in Anatomic Pathology and
Neuropathology at the Hospital of the University of Pennsylvania, after which she pursued post-doctoral
training under the mentorship of Dr. Edward B. Lee in the Translational Neuropathology Research Laboratory,
University of Pennsylvania. Currently, Dr. Nguyen is an assistant professor at Mayo Clinic Rochester, MN and
contributing neuropathologist to the Alzheimer’s Disease Research Center (ADRC) and Mayo Clinic Study of
Aging (MCSA). Dr. Nguyen’s long-term research focus is examining the role of microglia in cognitive resilience,
normal aging, and aging-related CNS diseases through integration of neuropathology and translational
research approaches to better understand neuroinflammation in human disease. This K08 award will provide
protected time to acquire expertise in integrating antemortem Alzheimer’s disease (AD) biomarkers and
neuropsychiatric data with postmortem neuropathology and to obtain expertise in two-photon in vivo imaging of
microglia in AD mouse models. Research will be performed under the mentorship of Dr. Prashanthi Vemuri, an
expert in cognitive resilience and neuroimaging, and Dr. LongJun Wu, an expert in microglial dynamics and
neuroimmune interactions using two photon in vivo imaging. This award will also provide protected time for Dr.
Nguyen to gain expertise through formal coursework, scientific seminars, and scientific meetings.
AD, neuropathologically defined by β-amyloid plaques and neurofibrillary tangles, progresses in a spatio-
temporally distinct fashion that can be studied in vivo by recent advances in neuroimaging and fluid
biomarkers. Several ante- and postmortem studies have shown a discrepancy between AD pathology extent
and cognition, forming the basis of cognitive resilience. A potentially protective microglial subpopulation termed
amyloid-responsive microglia (ARM) was previously described in a single-nuclei RNA sequencing study of
human AD brain. Whether microglial heterogeneity, specifically ARM, contribute to resilience is unclear. This
proposal leverages antemortem AD biomarkers, cognitive data, and postmortem tissue from MCSA
participants to address these specific aims: (1) Determine postmortem ARM tissue expression association with
antemortem fluid and neuroimaging biomarkers, and whether ARM may be predicted by biomarkers; (2)
Evaluate differential ARM tissue expression in cognitively resilient individuals versus not, and test antemortem
predictors; and (3) Examine ARM phagocytosis and effects on downstream neuronal dystrophy in the setting of
AD genetic risk. These studies will drive the development of an independent research program to study
microglial heterogeneity a...

## Key facts

- **NIH application ID:** 10884809
- **Project number:** 1K08AG081460-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Aivi Thanh Nguyen
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $155,520
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884809

## Citation

> US National Institutes of Health, RePORTER application 10884809, Role of Microglial Heterogeneity on Cognitive Resilience in Aging and Alzheimer’s Disease (1K08AG081460-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10884809. Licensed CC0.

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