# The Massachusetts and Yale ADRC Collaborative Proteomic Biofluid Biomarker Discovery Program

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $762,826

## Abstract

There are currently no practical biomarkers for Alzheimer’s Disease (AD) that can routinely
stage, assess prognosis, and monitor treatment response. AD is a complex disease of
overlapping pathophysiologies that lead to eventual synapse loss and progressive dementia.
The core AD biomarkers, amyloid-b and tau (total and phospho-) measured in cerebrospinal
fluid (CSF), provide a strong indication of the presence or absence of substantial AD pathology,
but as yet poorly reflect disease stage or progression. In order to diagnose the disease earlier,
learn about the time-course of concurrent pathophysiologies, and maximize the potential for
staging, tracking and treatment, it is critical that more useful AD biomarkers are characterized.
 A collaboration is proposed between the Yale and Massachusetts ADRCs that will leverage
the individual strengths of these two centers to discover pathway driven novel biomarkers of AD.
Using the large numbers of clinically characterized biofluid samples available from the
Massachusetts ADRC, the Yale ADRC will employ their expertise in quantitative targeted LC-
MS/MS technology to assess over one hundred analytes in CSF, with an extension of the most
informative to blood. LC-MS/MS is inherently specific, and enables simultaneous testing of
many markers from a small biofluid volume. Use of Data-Independent-Acquisition (DIA) LC-
MS/MS techniques allows for primary data to be reanalyzed for retrospective analysis of new
biomarkers, providing a reproducible yet flexible discovery pipeline.
 In Aim 1, a panel of over 100 proteins in CSF from pathways involved in AD
pathophysiology will be subjected to comprehensive technical qualification. Using samples from
the placebo arm of a clinical trial, peptides will be tested for linearity, inter-assay, intra-assay
and short term biotemporal stability. All high performing peptides will then be quantified in a
high contrast sample of 60 Cognitively unimpaired-adults (CU-A) and 60 dementia due to AD
cases. They will be assessed for their ability to distinguish AD from CU-A, and for their
correlation with markers of synaptic function. In Aim 2, technically qualified peptides will be
quantified in 3 tailored sample collections to assess their performance in AD staging, prognosis
and differential diagnosis. In Aim 3, the most informative analytes from Aims 1 & 2 will be
quantified in blood, either by LC-MS/MS, or by sensitive or ultra-sensitive ELISA approaches.
Peptide abundance will be compared across biofluids, and the diagnostic utility of these markers
in blood assessed.

## Key facts

- **NIH application ID:** 9936307
- **Project number:** 5R01AG062306-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** STEVEN E ARNOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $762,826
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936307

## Citation

> US National Institutes of Health, RePORTER application 9936307, The Massachusetts and Yale ADRC Collaborative Proteomic Biofluid Biomarker Discovery Program (5R01AG062306-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9936307. Licensed CC0.

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