# CSF, MRI, and PET biomarkers of neuroinflammation in Alzheimer's disease

> **NIH NIH R01** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2020 · $801,363

## Abstract

ABSTRACT
Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder. Inflammatory
changes in the brain are thought to represent key processes in the onset and progression of AD, but
it remains unclear whether neuroinflammation confers neuroprotection, accelerated degeneration, or
possibly both. Such an understanding in living humans is critical if we are to begin clinical trials using
the array of FDA-approved immunomodulatory drugs in the future. We propose that complement-
mediated neuroinflammation is protective in the early AD stages, while suppression of complement
activities is accompanied by the development of greater cognitive deficits and faster cognitive decline.
Our preliminary data from multiple cohorts support this hypothesis by showing 1) reduced levels of
cerebrospinal fluid (CSF) complement-related markers occur in the dementia stage but not mild
cognitive impairment (MCI) stage of AD; 2) reduced CSF complement-related markers and elevated
CSF interleukin-10 (IL-10) levels are associated with faster decline in AD; and 3) CSF inflammatory
protein alterations reveal networks of cellular and protein regulations. In the In the current
application, we will build on the association between complement related proteins and rates of
cognitive decline in AD to identify associated changes in soluble CSF cytokines and chemokines,
differential inflammatory cell type regulation, and imaging correlates of neuroinflammation. This
application takes advantage of our group’s strengths in performing CSF cytokine measurements, CSF
immunophenotyping, molecular imaging of neuroinflammation through positron emission tomography
(PET) and iron-enhanced MRI, and network analysis through a novel biochemical-bioinformatics
pipeline. We will directly identify individual and networks of soluble CSF cytokines that accompany
the transition from the MCI to the dementia stage of AD, correlate the complement and other altered
pathways with microglial activation through two modern PET tracers (11C-PBR28 and 18F-FEPPA),
and measure changes in individual T helper cell (type 1, 2, 17) and non-T cell populations. This
application represents the first attempt to correlate, at the individual level and at the group level, CSF
and imaging measures of neuroinflammation. If successful, this application will advance the
understanding of neuroinflammation in AD through parallel approaches, form the basis of a new
biomarker panel (and algorithm) to diagnose AD through a combination of degenerative and
inflammatory markers, and accelerate the target identification of future therapeutics aimed at
modulating the immune system in AD.

## Key facts

- **NIH application ID:** 10518656
- **Project number:** 7R01AG054046-06
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** William Tzu-lung Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $801,363
- **Award type:** 7
- **Project period:** 2016-08-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518656

## Citation

> US National Institutes of Health, RePORTER application 10518656, CSF, MRI, and PET biomarkers of neuroinflammation in Alzheimer's disease (7R01AG054046-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10518656. Licensed CC0.

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