# White matter degeneration: biomarkers in preclinical Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $760,068

## Abstract

ABSTRACT
Loss of myelinated axons is a feature of symptomatic Alzheimer's disease (AD). Our research group has also
detected degeneration of myelinated axons in the preclinical phase. A major theme of our ongoing work has
been to leverage the information derived from measures of myelin and axonal degeneration to improve the
understanding of AD. This is a renewal application for “White matter degeneration: biomarkers in preclinical
Alzheimer's Disease”. Participants comprise cognitively unimpaired adults from the Wisconsin Alzheimer's
Disease Research Center and the Wisconsin Registry for Alzheimer's Prevention who have been followed
longitudinally with neuroimaging and CSF collection. In this renewal application, we propose to continue to follow
enrolled participants as well as recruit additional participants to enrich for AD, including cognitively unimpaired
biomarker positive participants, individuals with mild cognitive impairment (MCI), and participants with dementia
due to AD. Participants will undergo comprehensive neuroimaging every two years. The hypothesis is that that
degeneration of myelinated axons is a critical facet of the AD process, and that measures of white matter
degeneration (myelin and axonal) can serve as sensitive markers of neurodegeneration in the context of plaque
and tangle accumulation. We will examine measures of axons, including the primary measures neurofilament
light protein in CSF and blood, and neurite density derived from multi-shell diffusion MRI. We will also evaluate
myelin via CSF biomarkers and quantitative myelin imaging with mcDESPOT MRI. Our three aims are to 1)
Define norms for white matter maturation/degeneration and determine the temporal ordering of AD pathology
and neurodegeneration, using quantile regression and pattern mixture modeling approaches, 2) Determine the
extent to which degeneration of myelinated axons predicts cognitive decline in the context of AD, and 3)
Determine the cause(s) of myelin and axonal degeneration. This program of research is expected to inform upon
the temporal course of AD development, disease severity, and the development of new treatment strategies.

## Key facts

- **NIH application ID:** 10390318
- **Project number:** 5R01AG037639-09
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Barbara Brigitta Bendlin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $760,068
- **Award type:** 5
- **Project period:** 2012-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390318

## Citation

> US National Institutes of Health, RePORTER application 10390318, White matter degeneration: biomarkers in preclinical Alzheimer's Disease (5R01AG037639-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10390318. Licensed CC0.

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