# Plasma brain-derived tau: a novel Alzheimer’s disease-type neurodegeneration biomarker with potential to complete the AT(N) scheme in blood

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $5,693,957

## Abstract

While the Amyloid(A)/Tau(T)/Neurodegeneration(N) framework has been validated against
neuropathology, cerebrospinal fluid (CSF) and neuroimaging biomarkers, its implementation in
blood is incomplete. We now have high-performance plasma A and T markers that become
abnormal according to AD pathophysiology. However, the current N marker – neurofilament light
(NfL) – is a non-disease-specific indicator of neurodegeneration/neuronal injury. Moreover,
plasma total-tau (t-tau) has large overlaps between diagnostic groups and does not correlate with
CSF t-tau. We have developed and validated a novel AD-type neurodegeneration biomarker
(referred to as brain-derived tau [BD-tau]) with capacity to complete the AT(N) framework in blood.
Our overall goal is to perform a large-scale clinical and pathophysiological validation of plasma
BD-tau. We will leverage five longitudinal, already existing, racially/ethnically diverse sporadic AD
cohorts (n = 2,594) with clinical, in vivo, and post-mortem evaluations to answer the following
specific aims: Aim 1. To compare associations of plasma BD-tau, NfL and t-tau with clinical
diagnosis of AD and longitudinal cognitive change; Aim 2. To compare AT(N) profiles and
associations for plasma BD-tau vs. NfL and t-tau; Aim 3. To compare the (added)
diagnostic value of plasma BD-tau vs. NfL and t-tau for autopsy confirmation of AD; and
Exploratory Aim 4: To compare performances of plasma BD-tau vs. NfL and t-tau in
different racial/ethnic groups. If proven, BD-tau will complete the AT(N) scheme in blood,
improving diagnostic and prognostic accuracies and confidence, as well as the prediction of
longitudinal cognitive change that are directly translatable to anti-AD clinical trials.

## Key facts

- **NIH application ID:** 10910143
- **Project number:** 5R01AG083874-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Thomas K Karikari
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $5,693,957
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910143

## Citation

> US National Institutes of Health, RePORTER application 10910143, Plasma brain-derived tau: a novel Alzheimer’s disease-type neurodegeneration biomarker with potential to complete the AT(N) scheme in blood (5R01AG083874-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10910143. Licensed CC0.

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