# Multimodal investigation of tau-related vasculopathy in prodromal Alzheimer's disease

> **NIH NIH K01** · UNIVERSITY OF WASHINGTON · 2021 · $121,607

## Abstract

Abstract
Research: Amyloid-beta (Ab) and tau represent the key pathological protein markers of Alzheimer’s Disease
(AD). Compared with Aβ, tau co-localizes more with sites of neurodegeneration and is more closely associated
with cognitive impairment. However, despite its pivotal clinical importance, mechanistic understanding of the role
of tauopathy in AD, including the associated pathophysiological effects leading to cognitive impairment, has been
elusive. Particularly, little is known about its relationship with the cerebrovascular dysfunction which is a critical
component in AD pathogenesis and neurodegeneration. This is especially true in prodromal AD patients.
Leveraging a state-of-the-art multimodal MRI/PET imaging approach, our proposal aims to address this gap and
disentangle the neuronal and vascular effects associated with tauopathy in prodromal AD. We propose to
investigate the regional association between tau deposition (measured using tau-PET) and two complementary
MRI markers of vascular system function: cerebral blood flow (CBF), and cerebrovascular reactivity (CVR). To
disentangle the vascular from the neuronal effects, we will also measure the regional glucose metabolism using
FDG-PET. We will then repeat the CBF and CVR measurements after 18-24 months to determine the relationship
between tau deposition and the temporal changes in CBF and CVR. The significance of this work is that it will
provide much richer and more specific information about underlying vascular pathology in prodromal AD than is
currently available and may emphasize for further developments of vasoprotective treatments. Our future work
will focus on identifying vascular mechanisms linking tauopathy to cognitive impairment and predicting the
pathological and cognitive trajectories of individual AD patients. Candidate: My long-term goal is to become an
independent investigator focused on neuroimaging research to create knowledge and tools for developing
effective therapies tailored to the individual characteristics of each AD patient. I have a strong technical
background in a wide range of MRI-based neuroimaging methods. Through this award, I will gain complementary
conceptual (pathophysiology and clinical aspects of AD) and technical (PET imaging, statistical modeling) skills,
which will enable me to formulate and test well-informed hypotheses for AD mechanisms. My short-term goals
are to 1) acquire in-depth knowledge about the pathology and biomolecular basis of AD, 2) acquire clinical
perspectives of AD, 3) develop proficiency in PET imaging and PET-based AD biomarkers, and 4) enhance my
skills in statistical longitudinal modeling. Environment: The unparalleled clinical and technical resources
available at the University of Washington Alzheimer’s Disease Research Center provide the ideal environment
for me to attain these goals. My exceptional mentoring team is comprised of senior faculty who are experts in
AD neuroimaging and have successfully mentored multip...

## Key facts

- **NIH application ID:** 10188424
- **Project number:** 1K01AG071798-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Hesamoddin Jahanian
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $121,607
- **Award type:** 1
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188424

## Citation

> US National Institutes of Health, RePORTER application 10188424, Multimodal investigation of tau-related vasculopathy in prodromal Alzheimer's disease (1K01AG071798-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10188424. Licensed CC0.

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