# Hyperphosphorylated tau aggregation kit to identify tauopathy risk factor

> **NIH NIH R44** · CAYMAN CHEMICAL COMPANY, INC. · 2020 · $778,104

## Abstract

PROJECT SUMMARY
Tauopathies are a group of neurodegenerative disorders sharing the common pathology of the tau protein
in the central nervous system. The most prominent tauopathy is Alzheimer’s disease (AD) that affects
nearly 6 million Americans and more than 30 million people worldwide. Additional tauopathies include
frontotemporal lobar degeneration with tau, Pick’s disease, progressive supranuclear palsy, and chronic
traumatic encephalopathy. Tauopathy patients suffer from progressive decline of cognitive and other
neurological functions. Clinical manifestations correlate with the spatiotemporal distribution of neuronal and
glial inclusions of abnormally phosphorylated tau (p-tau). Animal and cell studies demonstrated that soluble,
oligomeric p-tau are toxic to cells, and can transmit between cells by nucleating the pathological tau
aggregation in a prion-like fashion. Accordingly, molecules that inhibit or enhance the aggregation and
cytotoxicity of p-tau are potential therapeutics and risk factors, respectively. However, tau-centric drug
discovery has not come to fruition due primarily to the lack of a reliable and simple system for the synthesis
of pathologically relevant p-tau. During the course of a Phase I STTR grant (1R41AG057274), we used the
PIMAX system to synthesize four isoforms of p-tau bearing a core phosphorylation pattern highly relevant to
the disease. We developed kinetics assays for p-tau aggregation, and cell-based assays for the cytotoxicity
of p-tau. Importantly, we conducted a chemical library screen that identified both p-tau aggregation
inhibitors and enhancers that had been linked previously to dementia and Alzheimer's disease. These
achievements met and exceeded the milestones outlined in the original Phase I project. The goal of the
current Phase II SBIR project is to develop assay kits to support the identification of therapeutics and risk
factor of tauopathies, including Alzheimer's disease. In addition, using the cytotoxic p-tau synthesized in our
facilities, we will raise antibodies recognizing the pathogenic epitope of p-tau. If successful, this will lead to
the development of early diagnostic reagents and even novel tauopathy antibody therapies. By integrating
complementary and synergic expertise of teams from industry and academia, this SBIR project will have
solid impact on drug development, prevention, and diagnosis of Alzheimer’s disease and other tauopathies.

## Key facts

- **NIH application ID:** 10080823
- **Project number:** 2R44AG057274-02
- **Recipient organization:** CAYMAN CHEMICAL COMPANY, INC.
- **Principal Investigator:** MARIA INES MORANO
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $778,104
- **Award type:** 2
- **Project period:** 2017-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080823

## Citation

> US National Institutes of Health, RePORTER application 10080823, Hyperphosphorylated tau aggregation kit to identify tauopathy risk factor (2R44AG057274-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10080823. Licensed CC0.

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