# Relationships between blood-brain barrier breakdown, Alzheimer's disease pathology, and memory in aging

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $42,709

## Abstract

Project Summary
The major theory of causation for Alzheimer’s disease (AD) is deposition of the protein β-amyloid, however it is
unclear how aging influences amyloid accumulation or why cognitive decline can occur in its absence. Evidence
suggests that neurovascular dysfunction, such as the breakdown of the blood-brain barrier (BBB), is related to
neurodegeneration and cognitive impairment, and that this relationship may occur independently of amyloid.
However, the direct relationship between BBB breakdown and AD biomarkers, as well as cognition, has not been
thoroughly investigated in humans. The aim of this study is to use a novel multi-modal imaging design to examine
how BBB breakdown in humans is related to AD biomarkers of atrophy, amyloid and tau, and cognition. BBB
breakdown will be quantified in vivo using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI),
which allows for the detection of subtle BBB leakage in the human brain. Both tau and Aβ will be measured in
vivo using the positron emission tomography (PET) tracers [18F] Flortaucipir and [11C] PiB, respectively.
Neurodegeneration will be measured with structural MRI and episodic memory with a composite
neuropsychological test score. Aim 1 will determine if BBB breakdown increases with age and if there are specific
regions that are more vulnerable during normal aging. Aim 2 will examine if BBB breakdown in the temporal lobe
is related to greater global Aβ and regional tau. In addition, it will be determined if BBB breakdown is associated
with greater retrospective longitudinal Aβ and tau accumulation. Finally, Aim 3 will determine if BBB breakdown
in the temporal lobe is related to smaller temporal lobe volumes and worse memory performance. Relationships
between BBB breakdown and retrospective longitudinal change in memory performance, independent of amyloid
and tau, will also be examined. The findings from this study will help unravel fundamental mechanisms of AD
pathogenesis in the human brain, which has vital implications for early detection and the development of new
treatment strategies for AD. The proposed research project will achieve the applicant’s training goals, which
include (1) developing skills in multimodal imaging, (2) advanced statistics and data analysis training, (3) training
in clinical impairment and pathophysiology of AD, (4) development of teaching and mentoring skills, (5)
improvement of effective scientific communication skills, and (6) career development. UC Berkeley’s Helen Wills
Neuroscience Institute is home to a network of cutting-edge researchers and world-class imaging facilities. The
sponsor of the project, Dr. William Jagust, is at the forefront in applying multimodal neuroimaging methods to
study questions of aging and AD. He also has successfully mentored numerous students in the past, who have
become leaders in the field. The co-sponsor, Dr. Suzanne Baker, is an expert in optimization of neuroimaging
quantification for both PET and MRI...

## Key facts

- **NIH application ID:** 10387988
- **Project number:** 1F31AG072872-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Marisa Nicole Denkinger
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,709
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387988

## Citation

> US National Institutes of Health, RePORTER application 10387988, Relationships between blood-brain barrier breakdown, Alzheimer's disease pathology, and memory in aging (1F31AG072872-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10387988. Licensed CC0.

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