# Identifying microscopic vasculature within entorhinal cortex in healthy aging and its proximity to pathology profiles in Alzheimer's disease

> **NIH AG R01** · MASSACHUSETTS GENERAL HOSPITAL · 2026 · $699,509

## Abstract

Neuron death overwhelms the entorhinal cortex (EC) in Alzheimer’s disease (AD). Neuronal death, whether
with or without neurofibrillary tangle formation, is the pathology most strongly correlated with dementia. Poor
cerebrovascular health is a known risk factor in AD, but specific vascular territories within EC is not known. The
problem is that studies on pathologic biomarkers occur without the context of regional specificity, without
knowledge of the local vascular territories where vulnerable neuron populations reside, and clinical biomarkers
assess too late in disease progression. Moreover, neurodegeneration (neuronal death), as defined by the NIA-
AA framework, is vastly understudied. The field suffers from a disconnection between neuroimaging measures
and ground truth validation in the vulnerable entorhinal region. Identifying the microvascular pattern of local
penetrators and/or capillary bed for an EC subfield map, with total neuron counts, TDP-43, and tau burden is a
vital step to determining the heterogeneity in AD pathogenesis, vulnerability, or potential resilience. Aim 1 is to
image postmortem MRI to demonstrate microvascular arterioles, penetrators, and capillary beds in EC. High
field MRI at 7T will be used to produce the necessary high resolution with algorithms to enhance vessels. Aim
2 is to validate imaging with histologic vascular staining in EC, cross-referenced with tau, TDP-43, neuron loss.
Neuronal loss will be quantified with systematic random sampling stereology counting methods and
immunohistochemistry will be used for pathology profiles. Aim 3 is to apply pathology maps, vascular territories
map, to large existing in vivo MRI datasets, ADNI, HABS, and HCP. The overall goal is to identify a unique
vascular pattern within EC in controls and demonstrate EC subfield vascular territories with neuronal
vulnerability. The deliverables in this proposal will be the juxtaposition of vascular, tau, TDP-43, and neuronal
loss data validated in human ti

## Key facts

- **NIH application ID:** 11457052
- **Project number:** 4R01AG082223-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jean  Augustinack
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AG
- **Fiscal year:** 2026
- **Award amount:** $699,509
- **Award type:** 4N
- **Project period:** 2023-04-15T00:00:00 → 2028-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11457052

## Citation

> US National Institutes of Health, RePORTER application 11457052, Identifying microscopic vasculature within entorhinal cortex in healthy aging and its proximity to pathology profiles in Alzheimer's disease (4R01AG082223-02). Retrieved via AI Analytics 2026-07-02 from https://api.ai-analytics.org/grant/nih/11457052. Licensed CC0.

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