# Profiling Alzheimer's Biomarkers

> **NIH VA I01** · EDITH NOURSE  ROGERS MEMORIAL VETERANS HOSPITAL · 2021 · —

## Abstract

Abstract
 With our unique multi-component clinical sample and advances in Mass Spectrometry (MS), we hope to
identify a combination of multiple biomarkers that provide discriminatory and accurate biomarkers of
Alzheimer’s disease (AD) to advance earlier detection and treatment. Currently, the ratio of tau/Aβ in
cerebrospinal fluid (CSF) is the best available biomarker for separating AD from normal subjects and predicting
disease progression, but its sensitivity and specificity are modest. Our co-investigator (co-I), Dr. Lu, discovered
that a pathologic conformation, the cis-form of phosphorylated pT231-tau (cis-ptau), contributes to AD
pathogenesis. Similarly, oligomeric Aβ (oAβ) is the most toxic form of Aβ to neurons, and we found that oAβ
was increased in plasma and brain tissue of AD patients. Our hypothesis is that detection of increased levels of
these pathologic species (cis-ptau and oAβ) will yield a robust biomarker for AD. Our team is uniquely
positioned to test this hypothesis. We are the first group who reported MS-based proteomic profiling of three
dimensional (3D) neuronal culture. We have analyzed candidate biomarkers from the plasma, induced
pluripotent stem cells (iPSC) derived neurons, and post-mortem brain tissue from the same AD patients, which
is unprecedented. We have analyzed brain tissue from 10 cases out of 20 AD, 20 MCI and 20 non-demented
(ND) subjects from VA Bedford/Boston University Alzheimer Disease Center (ADC) Brain Bank (directed by co-
I, Dr. Stein). Our biomarker detection capability is well-developed and we have in hand a clinically well-
characterized set of plasma, CSF, and brain samples. We will validate novel biomarkers using the test samples
of plasma and CSF from the same patients with early and moderate AD (20 patients) and 20 control ND
subjects from Wisconsin ADC (samples are currently stored in co-I Dr. Lu’s lab). We will first determine
whether CSF cis-ptau alone sufficiently separates AD from ND subjects. Next, truncated A peptides will be
measured along with cis-ptau to determine whether ratios of cis-ptau/A in CSF provides a better separation of
AD from ND subjects. Finally, we will quantify plasma cis-ptau and plasma oAβ, and use a combination of
plasma cis-ptau and oAβ along with CSF cis-ptau as biomarkers for AD.

## Key facts

- **NIH application ID:** 10084221
- **Project number:** 5I01BX003527-04
- **Recipient organization:** EDITH NOURSE  ROGERS MEMORIAL VETERANS HOSPITAL
- **Principal Investigator:** Weiming Xia
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-10-01 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084221

## Citation

> US National Institutes of Health, RePORTER application 10084221, Profiling Alzheimer's Biomarkers (5I01BX003527-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10084221. Licensed CC0.

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