# Integrated Platform to study Neurodegeneration in Alzheimer’s Disease

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2022 · $778,347

## Abstract

Project Summary/Abstract
In Alzheimer's disease (AD), the accumulation of intracellular posttranslationally modified Tau aggregates, is a
hallmark of AD pathology and a strong correlate of cognitive impairment. While the dozen or so
Posttranslational Modifications (PTMs) on Tau in pathological aggregates have been studied for decades, our
new quantitative and qualitative mass spectrometry approaches have discovered ~100 PTMs in the angular
gyrus from 98 human Alzheimer's Disease patients in these aggregates, i.e. Braak stages V/VI, and age
matched control subjects without pathological changes in the frontal lobe. In this proposal, we aim to develop
a large-scale proteomics platform to map the temporal occurrence of PTMs as disease progresses. We will
examine a valuable new set of cases, selected to encompass all Braak stages from 0 to VI. All cases in this
new cohort will have detailed premortem clinical data, which will allow us to detect and assess correlations
between clinical and pathophysiological findings and any tau PTM that is identified in this study. For this
analysis, we will study 3 brain regions (entorhinal/amygdala, and temporal and visual cortex) in 20 Braak 0
subjects; 40 early stage Braak I/II subjects; 40 mid stage Braak III/IV subjects; and 40 end stage Braak V/VI
subjects. We will also map the global proteomes of the brain specimens from this well-characterized patient
cohort to identify the enzymes associated with these Braak stage dependent PTMs. The findings of the tau
characterization and mapping of the proteomes will be validated using widely accepted Tau sensor assays
used to study Tau aggregation in AD.
In summary, this Tau PTM specific dataset, the deep proteome maps and the subsequent validation
experiments in seeding assays will be used to test our overarching hypothesis: Understanding how the
progressive accumulation of Tau PTMs results in the toxicity and seeding competence of tau, and mapping the
disease progression dependence of these PTMs and the enzymes responsible for them will allow us to develop
interventional strategies at earlier and prodromal stages of disease.

## Key facts

- **NIH application ID:** 10380779
- **Project number:** 5R01AG071858-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Judith A Steen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $778,347
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380779

## Citation

> US National Institutes of Health, RePORTER application 10380779, Integrated Platform to study Neurodegeneration in Alzheimer’s Disease (5R01AG071858-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380779. Licensed CC0.

---

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