# Core C - Human Consultation-Biosamples-Biomarkers Core

> **NIH NIH P01** · UNIVERSITY OF KENTUCKY · 2022 · $414,511

## Abstract

CORE C: HUMAN CONSULTATION, BIOSAMPLES, BIOMARKERS (CBB)
ABSTRACT
The Human Consultation, Biosamples, Biomarkers (CBB) Core (Core C) will complement and integrate the
Projects of the P01 Strategies for Targeting Reactive Astrocytes in AD and ADRD. It is critical to validate
the translational relevance of mechanistic mouse models, and to extend those results toward further clinical
studies. Yet there are challenges when it comes to addressing the complex pathobiology of the dementia clinical
syndrome. Core C will bridge those critical gaps through the following Specific Aims: Aim 1: Optimize
clinically-relevant study design and manage ongoing data streams incorporating human biomarker and
autopsy data. This Aim will foster integration, organization, coherence, and documentation for Core C. The
multimodal data include molecular, metabolic, and network-wide domains in human endophenotypes, and
human preclinical and clinical endpoints. Aim 2: From existing autopsy material and data, generate a set
of human cases from the UK-ADRC that encompasses the AD/ADRD phenotypes studied in all 4
Projects (AD, VCID, LATE+HS, and controls) and provides a common basis for downstream biochemical
and neuropathological endpoint assessments relevant to the Projects. We will analyze a panel of 100
cases for this Aim. Aim 2a: Biochemistry. We will perform multi-level protein extracts and run immunoblots
with quantitative measurements on each sample with astrocytic proteins (e.g., AQP4, Kir4.1, GFAP, SLC1A2,
ABCC9/SUR2, Insulin receptor) being studied in the Projects. We will separately assess snap-frozen
hippocampal samples, as well as frontal cortex (Brodmann Area 9) white matter and gray matter seperately.
Aim 2b: Neuropathology. Neuropathologic endpoints will be characterized in a quantitative manner in the
same panel of 100 cases: Astrocytosis (GFAP+), Aβ plaques, TDP-43 proteinopathy, and Tau tangles. We
also will perform highly quantitative assessments of blood vessel morphology using CD34 (capillaries) and ?-
SMA (arteriole) markers. Double-label IFC will characterize IR and SUR2 proteins’ cellular distributions.
Samples will also be genotyped for ABCC9 risk alleles. Aim 3: From existing clinical outcome measures,
generate a set of biomarker (in vivo) data from human participants that represents a common basis for
downstream biofluids and neuroimaging endpoint assessments relevant to the projects. Aim 3A:
Neuroimaging. A 3D anatomical magnetization-prepared rapid acquisition with gradient echo (MPRAGE),
cerebrovascular reactivity (CVR), from existing human imaging on a 3T MRI scanner will be generated and
provided to Projects and Core D. Drs. Powell and Bahrani in Core C are also performing parallel neuroimaging
experiments in mice (Core B). Aim 3B: Fluid Biomarkers. Cerebrospinal fluid (CSF) and plasma that are
banked from UK-ADRC and UK-MarkVCID participants will be assayed for MMP9 and GFAP using Quanterix
Simoa assays and AQP4, Kir4.1 and Dp71 will be assayed...

## Key facts

- **NIH application ID:** 10495933
- **Project number:** 1P01AG078116-01
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** PETER T. NELSON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $414,511
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10495933

## Citation

> US National Institutes of Health, RePORTER application 10495933, Core C - Human Consultation-Biosamples-Biomarkers Core (1P01AG078116-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10495933. Licensed CC0.

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