# Temporal sequence, anatomic progression, and interaction of amyloid-beta and tau (Project 1)

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $238,731

## Abstract

SUMMARY: PROJECT 1- AMYLOID AND TAU PET
Trajectories of aβ and tau deposition can now be related to each other and to other biomarkers of preclinical
AD as well as to clinical endpoints. Recent therapeutic trial failures highlight the critical need for a better
understanding of how changing levels of pathology relate to each other and to clinical outcomes. Unfortunately,
these relationships are complex, and optimized measures permitting robust tracking of dynamics remain
underdeveloped, posing a barrier to efficient, rapid progress toward successful therapeutics. Initial study of
these trajectories in HABS indicated that earlier aβ increase was detectable but was not associated with
cognitive decline until a later observation period, during which time the decline was mediated by concurrent
measures of tau accumulation. In the proposed HABS Cycle 3, Project 1 will focus on the progression and
interrelated dynamics of aβ and tau pathologies assessed with PET acquired in the Imaging Core to identify
stages of pathologic progression. We will leverage the HABS sample, with 9 years of amyloid and 4 years of
tau PET follow up along with longitudinal neuropsychological data to characterize stages of progression in
terms of time (Aim 1) and space (Aim 2), as well as explore novel plasma measures for manifestations of these
stages (exploratory Aim 3). Specifically, HABS participants will undergo serial imaging with 11C Pittsburgh
Compound B and 18F Flortaucipir PET with Aim 1, to characterize the temporal trajectory of each pathology,
relate these trajectories to each other, identify dynamic connections between each that progress in successive
intervals, and relate these findings to age, sex, and APOE genotype; Aim 2, to identify the specific anatomy of
aβ and tau progression based on serial measures; and Aim 3 (Exploratory), investigate the associations of aβ
and tau level and change measured with PET to measures obtained with blood biomarkers, and to correlate
findings with autopsy brains as they become available. Project 1 will contribute to the overall Program goals:
together we will assess the impact of modulating factors (Project 2) as well as the functional links (Project 3)
that relate pathologic change to clinical phenotype (Project 4). Together, this research will ultimately improve
sampling for clinical trials and therapeutic targeting strategies.

## Key facts

- **NIH application ID:** 10144908
- **Project number:** 5P01AG036694-12
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Keith A. Johnson
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $238,731
- **Award type:** 5
- **Project period:** 2010-07-15 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144908

## Citation

> US National Institutes of Health, RePORTER application 10144908, Temporal sequence, anatomic progression, and interaction of amyloid-beta and tau (Project 1) (5P01AG036694-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10144908. Licensed CC0.

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