Quantification of white matter cellularity and damage in preclinical and early symptomatic Alzheimer's disease
Open accessAbstract
Interest in understanding the roles of white matter (WM) inflammation and damage in the pathophysiology of Alzheimer disease (AD) has been growing significantly in recent years. However, in vivo magnetic resonance imaging (MRI) techniques for imaging inflammation are still lacking. An advanced diffusion-based MRI method, neuro-inflammation imaging (NII), has been developed to clinically image and quantify WM inflammation and damage in AD. Here, we employed NII measures in conjunction with cerebrospinal fluid (CSF) biomarker classification (for β-amyloid (Aβ) and neurodegeneration) to evaluate 200 participants in an ongoing study of memory and aging. Elevated NII-derived cellular diffusivity was observed in both preclinical and early symptomatic phases of AD, while disruption of WM integrity, as detected by decreased fractional anisotropy (FA) and increased radial diffusivity (RD), was only observed in the symptomatic phase of AD. This may suggest that WM inflammation occurs earlier than WM damage following abnormal Aβ accumulation in AD. The negative correlation between NII-derived cellular diffusivity and CSF Aβ42 level (a marker of amyloidosis) may indicate that WM inflammation is associated with increasing Aβ burden. NII-derived FA also negatively correlated with CSF t-tau level (a marker of neurodegeneration), suggesting that disruption of WM integrity is associated with increasing neurodegeneration. Our findings demonstrated the capability of NII to simultaneously image and quantify WM cellularity changes and damage in preclinical and early symptomatic AD. NII may serve as a clinically feasible imaging tool to study the individual and composite roles of WM inflammation and damage in AD.
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Dysfunction of oligodendrocytes and myelin breakdown may be early events in AD.
“Dysfunction of oligodendrocytes and myelin breakdown may be early events in AD72–75.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [75]
The Discussion (page unavailable) describes demyelination in early symptomatic AD, supporting the myelin-breakdown part of the claim. But the Results found no myelin-related imaging differences in preclinical AD, and the Introduction mentions oligodendrocyte reduction only in TREM2-deficient mice, not oligodendrocyte dysfunction as an early event in human AD. (LLM, conf=0.84)
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- Authors
- Wang, Q., Wang, Y., Liu, J., Sutphen, C. L., Cruchaga, C., Blazey, T., Gordon, B. A., Su, Y., Chen, C., Shimony, J. S., Ances, B. M., Cairns, N. J., Fagan, A. M., Morris, J. C., & Benzinger, T. L. S.
- Affiliations
- Washington University in St. Louis (US)
- Banner Alzheimer’s Institute (US)
- Corresponding author
- Wang, Yong
- ORCID
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2019
- Volume
- 22
- Pages
- 101767
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC6428957
- OpenAlex
- W2922178832
- Cited by
- 63
- References
- 24
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 11 · 2023: 13 · 2022: 10 · 2021: 5 · 2020: 5 · 2019: 1
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Center for Advancing Translational Sciences (5P30NS048056)
- National Institute on Aging (P01AG003991, 1R01AG054567-01A1, P50AG05681, P01AG026276)
- National Multiple Sclerosis Society (RG5265 A1)
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Institute of Clinical and Translational Sciences
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, white matter inflammation, white matter injury, preclinical Alzheimer's disease, amyloid-beta, cerebrospinal fluid biomarkers, tau protein, fractional anisotropy, radial diffusivity, white matter integrity, neurodegeneration
- MeSH terms
- Aged, Alzheimer Disease, Female, Humans, Image Processing, Computer-Assisted, Inflammation, Longitudinal Studies, Male, Middle Aged, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, Diffusion Magnetic Resonance Imaging, Prodromal Symptoms, White Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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