# Core B - Biomarkers

> **NIH NIH P01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $239,634

## Abstract

CORE B – PROJECT SUMMARY/ABSTRACT
The Biomarker Core B will continue to provide services, resources and expertise in blood-brain barrier (BBB)
and neurovascular unit (NVU) and AD (Aβ, tau, pTau) biomarkers in CSF and plasma for Projects 1-3 and all
P01 investigators. This includes biomarkers in individuals at high genetic risk for AD (APOE4 carriers) and in
those at the lower risk for AD (APOE3 homozygotes) (Projects 1 and 2), and in novel APOE knock-inflox/flox (KIF)
mouse lines with and without A and tau pathology (Project 3). The core will provide the essential, quantified
molecular measures relatable to the imaging and cognitive measures collected as part of this program. During
the initial P01’s budget period, Core B has developed and tested a novel panel of 37 BBB/NVU biomarkers
measured simultaneously with A and tau biomarkers in >800 CSF human samples. The data have been used
by Projects 1 and 2 in several high impact publications by P01 Investigators. The CSF BBB/NVU and AD
biomarkers have been validated by site-specific analysis from multiple P01 sites. For Projects 1 and 2, Core B
has recently tested a group of biomarkers in human plasma (e.g., sPDGFR, A40/A40, total tau, pTau-181),
and is developing additional BBB/NVU biomarkers in plasma (e.g., BBB tight junction proteins, S100B, sTREM2).
For Project 3, Core B has developed and validated all proposed 30 BBB/NVU biomarkers in the mouse CSF
and plasma, using transgenic pericyte-deficient, APOE knock-in, 5xFAD and/or P301S tau lines. The mouse
BBB/NVU and AD biomarkers are analogous to the respective human biomarkers, which allows us to directly
compare findings in humans (Projects 1 and 2) and mice (Project 3). Existing strengths of Core B include: 1)
decades of experience and knowledge in studying the BBB, NVU, and cerebrovascular system; 2) several years
of experience working with MSD (Mesoscale Discovery Technology) scientists to develop the first reliable
simultaneous measurements of multiple BBB/NVU biomarkers in biofluid samples in humans and mice including
development of new MSD assays for sPDGFR, CypA, MMP9, sLRP1; 3) established and validated
collaboration with all clinical site co-Is participating in this P01 including USC ADRC (Chui, Schneider, Ringman,
Joe, Yassine), Huntington Medical Research Institute Pasadena (Harrington), Washington University Knight
ADRC (Morris, Fagan, Benzinger), Banner Alzheimer’s Institute (Reiman)/ Mayo Clinic Arizona (Caselli), as well
as with Project 1- 3 Investigators – laboratories of Drs. Zlokovic, Nation, Pa, Toga, Thompson, Jacobs, Coba,
Holtzman and Griffin. For most BBB/NVU biomarkers in human (Project 1, 2) and mouse (Project 3) biofluids,
Core B will use MSD multiplex or singleplex platforms; and for a few biomarkers ELISA and Sima (see Res. Plan
Fig. 2). Under the leadership of Dr. Zlokovic and the resources available at the Zilkha Neurogenetic Institute at
USC, Core B will continue to 1) coordinate biofluid collection, processi...

## Key facts

- **NIH application ID:** 10331682
- **Project number:** 2P01AG052350-06
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Berislav V Zlokovic
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $239,634
- **Award type:** 2
- **Project period:** 2016-09-30 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331682

## Citation

> US National Institutes of Health, RePORTER application 10331682, Core B - Biomarkers (2P01AG052350-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10331682. Licensed CC0.

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