# Systemic- and neuroinflammation and the progression of Alzhemer's disease

> **NIH NIH K23** · JOHNS HOPKINS UNIVERSITY · 2020 · $173,378

## Abstract

Project Summary
The goal of this K23 application is to provide a tailored program of mentored research training for Dr. Keenan
Walker, a neuropsychologist in the Department of Neurology at Johns Hopkins University School of Medicine.
Over the last several years, Dr. Walker has positioned himself to become a leader in the field of Alzheimer’s
disease research, with particular expertise in understanding the mechanistic connection between aberrant
immune functioning, cognitive decline, and Alzheimer’s disease. Dr. Walker seeks a Career Development
Award to obtain mentored research experience, new skills, and content knowledge that are critical to
advancing his career as an independent investigator. The research plan outlined in this application leverages
existing data from the Atherosclerosis Risk in Communities (ARIC) study with novel methods to examine the
association of discrete systemic- and neuro-inflammatory pathways with components of Alzheimer’s disease
pathogenesis in a community sample of non-demented older adults. There is currently no consensus as to
whether neuroinflammation takes on a protective or pathological role in the preclinical and mild cognitive
impairment (MCI) phase of Alzheimer’s disease. Relatedly, it is unclear whether systemic pro- and anti-
inflammatory signaling may influence the activation of neuroinflammatory pathways, or the progression of β-
amyloid (Aβ) deposition. The proposed research uses stored blood specimens to determine whether systemic
pro- and anti-inflammatory signaling is associated with longitudinal change in Aβ deposition (as measured by
PET), MRI-defined neurodegeneration, and cognitive decline in a large group (N=1,000) of non-demented
older adults within the ARIC cohort (Aim 1). Using novel methods to measure the contents of astrocyte-derived
exosomes (ADEs) in a subset of participants (N=500), this study will also determine whether the activity of
discrete astrocytic neuroinflammatory pathways (e.g., complement, and cytokine signaling) relates to
subsequent Aβ accumulation, neurodegeneration, and cognitive decline (Aim 2). Lastly, this study will examine
how these markers of systemic- and neuro-inflammation relate to 18-kDa translocator protein (TSPO) PET
measures of microglial activation in a small sample of adults with MCI (Aim 3). This K23 will support Dr. Walker
in pursuit of his training goals, which include (1) acquiring the skills and knowledge necessary to use
exosomes for the study of molecular pathways relevant to Alzheimer’s disease, (2) gaining proficiency with
PET imaging as a research tool for the study of Aβ deposition and neuroinflammation, and (3) developing an
advanced understanding of relevant immunological and neuro-immunological principles. To achieve these
training goals, Dr. Walker has established a multidisciplinary team of world-renowned mentors and
collaborators with expertise in Alzheimer disease, neuroimmunology, aging biology, and molecular imaging.
This training plan w...

## Key facts

- **NIH application ID:** 9988324
- **Project number:** 5K23AG064122-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Keenan Alexander Walker
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $173,378
- **Award type:** 5
- **Project period:** 2019-08-15 → 2020-10-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988324

## Citation

> US National Institutes of Health, RePORTER application 9988324, Systemic- and neuroinflammation and the progression of Alzhemer's disease (5K23AG064122-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9988324. Licensed CC0.

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