# Michigan Alzheimer’s Disease Research Center-Supplement

> **NIH NIH P30** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $500,223

## Abstract

ABSTRACT – SUPPLEMENT
We seek to define the MR correlates of white matter histopathological features in Alzheimer’s disease and
related disorders (ADRD) by combining the resources at MADRC Neuropathology core, with its repository of
post-mortem frozen tissue with a wealth of accompanying pre-mortem MR studies, with the resources of
MADRC Neuroimaging core and its advanced MR facility comprised of experts in the fields of MR acquisition,
post-processing, and parameterization. Post-mortem histological studies and pre-mortem imaging studies
indicate that multiple pathologies often co-exist and that single pathologies are often the exception, as
demonstrated by the frequent presence of brain lesions of presumed vascular origin, such as white matter
(WM) lesions, microbleeds, and microinfarcts. The clinical significance and the degree to which such lesions
contribute to clinical decline is unclear, partly because routine MRI techniques such as T1 and T2 weighted
imaging lack the specificity to further characterize their pathological underpinnings such as demyelination,
gliosis, or axonal loss. Guided by pre-mortem MR studies of donors with a diagnosis of vascular dementia
(VD), Alzheimer’s disease (AD), and neurologically intact donors (ND), we will analyze frozen post-mortem
tissue both from brain regions surrounding LPVO’s and brain regions without any T2 abnormalities. We will
obtain advanced MR (MWF, ihMT, and multi-shell, multi-directional diffusion) parameters from these tissue
blocks as well as conventional T1-weighted and T2-weighted MRI’s at 7T. Tissue fixation,
histological/immunohistochemical techniques, and light-microscopy will be used to classify and quantify the
presence of various pathological parameters, including myelin density, microglia proliferation, oligodendrocyte
density, phosphorylated tau, tissue iron content, vessel wall thickness, and amyloid deposition. Our goal is to
characterize the MR signature patterns that correlated with various pathological features in white matter
abnormalities. Defining the multi-modal MR signatures that correlate with ominous histopathological features,
and the relationship between pathological diagnosis and MR signal in the normal-appearing white matter will
allow us to disentangle MR features that reflect pathological changes driving cognitive decline from those that
are related to other factors such as aging. Establishing this histo-radiological link will sharpen the focus of in-
vivo MR methods and allow their incorporation in future studies to more precisely monitor and predict cognitive
decline in ADRD. In addition to its non-amyloid approach, this proposal brings together resources of multiple
cores at MADRC and involves the expertise from three major universities in Michigan, each with its own set of
skill sets to drive the project forwards. In addition, the raw data from these efforts will be shared among other
centers to allow for future collaborative work in the field.

## Key facts

- **NIH application ID:** 10599387
- **Project number:** 3P30AG072931-02S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Henry L Paulson
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $500,223
- **Award type:** 3
- **Project period:** 2021-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599387

## Citation

> US National Institutes of Health, RePORTER application 10599387, Michigan Alzheimer’s Disease Research Center-Supplement (3P30AG072931-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10599387. Licensed CC0.

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