# Evaluation of the neurovascular unit in the setting of pathogenesis and treatment of autosomal dominant Alzheimer disease

> **NIH NIH K01** · WASHINGTON UNIVERSITY · 2024 · $94,049

## Abstract

PROJECT SUMMARY
The overall objective of this proposal is to support the candidate’s career development and transition to that of
an independent researcher. The outlined training plan will equip the applicant with the necessary skills to
conduct innovative research in a rich, interdisciplinary, and collaborative environment, facilitating the
investigation of new avenues of clinical research and trials. By utilizing multimodal imaging techniques and
molecular and cellular proteomic approaches, the candidate will reinforce an already strong background in
neuroimaging, learn and integrate new approaches to gain a greater holistic understanding of Alzheimer
disease (AD) etiology and pathophysiology, and contribute to the success of potential new therapies for AD. β-
amyloid (Aβ), one of the earliest biomarkers to accumulate during AD progression, is the most targeted factor
for therapeutic intervention. However, other components, such as vascular and inflammatory/immune changes,
also occur during AD progression, adding to the complexity of fully characterizing AD pathogenesis. The
neurovascular unit (NVU) is relevant to the study of vascular, immune, and Aβ changes in AD, as it comprises
neuronal-astrocyte signaling and the blood-brain barrier, which play a role in Aβ clearance. Age-related
comorbidities in late-onset AD (LOAD) are challenging to distinguish from AD-related changes involved in the
progression of the disease. This proposal aims to disconnect age- from disease-related changes to vascular
and immune components and to understand the impact of these disease-related changes on anti-Aβ treatment
outcomes. This will be accomplished by studying these factors in autosomal dominant AD (ADAD), a rare form
of AD with a known genetic etiology and with early age of symptom onset. Previous studies utilizing proteomic
approaches and imaging to assess NVU disruption have focused on LOAD populations. The goal of Aim 1 of
this proposal is to assess changes in the NVU in known carriers of ADAD-related mutations and with markers
of vascular changes and generate a proteomic profile of NVU changes. The goal of Aim 2 is to define the
temporality and association of NVU disruption relative to other established markers of disease progression.
The goal of Aim 3 is to define the influence of NVU disruption on outcomes of Aβ clearance therapies, as well
as on the incidence of treatment side effects and the association with primary clinical and cognitive outcomes.
Successful completion of this proposed research project will improve our understanding of the vascular- and
immune-related processes involved in AD and their relationship with Aβ, the pathophysiology of AD, and their
influence on treatment-related Aβ changes.

## Key facts

- **NIH application ID:** 10788327
- **Project number:** 5K01AG080123-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Nelly Cecile Joseph-Mathurin
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $94,049
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10788327

## Citation

> US National Institutes of Health, RePORTER application 10788327, Evaluation of the neurovascular unit in the setting of pathogenesis and treatment of autosomal dominant Alzheimer disease (5K01AG080123-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10788327. Licensed CC0.

---

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