# The Longitudinal Course O\F Imaging Biomarkers in People At RISK of AD

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $1,802,518

## Abstract

The goal of this ongoing R01 is to chart the progression of pathobiologic markers of presymptomatic
Alzheimer's Disease (AD) and their effect on neural function and cognition in a late-middle-aged cohort
enriched with risk for AD. There is an appreciable gap in knowledge about the temporal disease course in this
age range that this ongoing project has been directly addressing with serial multimodal imaging including
amyloid, cerebrospinal fluid (CSF) collection, and serial cognitive measurement. In the next funding cycle we
will add a new positron emission tomography (PET) imaging technique sensitive to fibrillar tau [F-18]THK5351
indexing neurofibrillary pathology. In the prior funding period we recruited 179 individuals from a registry of
1,545 people at risk for AD known as WRAP (Wisconsin Registry for Alzheimer's Prevention). We found that
[C-11]PIB amyloid burden is detectable in 20% of people with parental history of AD at a mean age of 60.
Baseline amyloid is more extensive in the presence of higher CSF total tau levels, and 2-year increases in PiB
amyloid are significantly predicted by higher baseline CSF tau. The hypothesis for this renewal is that tau-
related neurofibrillar pathology begins early (in accord with the neuropathology literature) in people at AD risk
and its strategic spatial burden explains changes in amyloid, neural function and cognitive decline. Aim 1: To
test the premise that amyloid burden is necessary but not sufficient to evoke preclinical cognitive change. We
will examine effects of longitudinal amyloid and tau change on episodic memory trajectories over time in 235 at
risk individuals including all subjects we previously enrolled and follow them over 2 years with advanced
multimodal imaging and CSF. Aim 2: To assess the effects of tau and amyloid imaging on MRI and CSF
indicators of neural injury and function. Aim 3: To develop a multimodal disease marker to maximize efficiency
of clinical trials in preclinical AD. Following our work in creating tools for efficient clinical trials in MCI, we will
extend these concepts to the pre-MCI phase of disease utilizing deep learning architectures with tau, amyloid
and structural imaging inputs. We will also examine change over time in tau, amyloid and cognition as
outcomes. As any of these features considered singularly may be affected by age, and as amyloid and tau may
be `necessary but not sufficient' by themselves, a derived multimodal marker may have eventual clinical utility
in enriching prevention trials with those most likely to progress, and increasing power to detect change
attributable to preclinical interventions. Significance: Relative tau and amyloid imaging profiles have not been
empirically established in the presymptomatic time frame and this information is urgently needed to identify
incipient disease. No comparable studies exist regarding the evolution of tau and amyloid signal in the critical
late-middle-age time frame of preclinical AD. This ongoing pro...

## Key facts

- **NIH application ID:** 9919506
- **Project number:** 5R01AG021155-15
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Sterling C Johnson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,802,518
- **Award type:** 5
- **Project period:** 2004-08-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9919506

## Citation

> US National Institutes of Health, RePORTER application 9919506, The Longitudinal Course O\F Imaging Biomarkers in People At RISK of AD (5R01AG021155-15). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9919506. Licensed CC0.

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