# Staging Alzheimer disease with blood-based biomarkers

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $689,321

## Abstract

The brain changes of Alzheimer disease (AD) start many years before the onset of cognitive symptoms. Most
models of AD propose a stepwise progression of brain pathology starting with amyloid plaque deposition, then
tau tangle formation, then neurodegeneration. Cerebrospinal fluid (CSF) and imaging biomarkers have been
developed that allow detection of AD brain pathology in living individuals, but these modalities have significant
drawbacks that limit their widespread use. Over the last three years, there has been rapid development of
blood-based biomarkers that accurately detect AD brain pathology. In this study, we propose to study
some of the most promising blood-based biomarkers for three types of AD brain pathology: amyloid
(Aβ42/Aβ40), tau (phosphorylated tau [pTau] isoforms), and neurodegeneration (neurofilament light
chain protein [NfL]). The research team has developed immunoprecipitation-mass spectrometry assays for
plasma Aβ42/Aβ40 and pTau isoforms that will be further optimized and automated as part of the proposed
project. The Knight Alzheimer Disease Research Center cohort will be studied, and has available data on
plasma and CSF NfL, clinical dementia diagnosis, performance on cognitive tests, health history, amyloid PET,
tau PET, structural brain volumes by MRI, genetic markers, numerous CSF biomarker measures, discovery
proteomics data, and autopsy reports. Approximately 1,700 matched pairs of banked plasma and CSF
samples from ~1,000 individuals will be examined, which is similar in size to recent major studies of cognitive
outcomes as a function of biomarker combinations. The correlation of the blood-based measures with better
established CSF and imaging measures will be evaluated. Biomarkers of amyloid, tau and neurodegeneration
will be used independently and in combination within a modality (blood-based, CSF or imaging) to predict the
risk for current or future symptomatic AD. For all analyses, the effects of individual characteristics (including
age, sex, years of education, APOE ε4 genotype, polygenic risk score, race, and medical comorbidities) will be
evaluated to identify factors that modify the expression of symptoms associated with biomarker levels. We
hypothesize that the combination of plasma Aβ42/Aβ40, pTau isoforms and NfL will perform better than
amyloid PET in predicting risk for current or future symptomatic AD. Because blood tests are well-accepted by
patients, physicians, and researchers, an accurate blood test for symptomatic AD would likely be widely used
and could be a game-changer in improving AD research, accelerating clinical trials and enabling more accurate
diagnoses in the clinic.

## Key facts

- **NIH application ID:** 10775754
- **Project number:** 5R01AG070941-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Suzanne Elizabeth Schindler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $689,321
- **Award type:** 5
- **Project period:** 2021-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10775754

## Citation

> US National Institutes of Health, RePORTER application 10775754, Staging Alzheimer disease with blood-based biomarkers (5R01AG070941-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10775754. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*