White matter changes in Alzheimer’s disease: A focus on myelin and oligodendrocytes
Open accessAbstract
Alzheimer's disease (AD) is conceptualized as a progressive consequence of two hallmark pathological changes in grey matter: extracellular amyloid plaques and neurofibrillary tangles. However, over the past several years, neuroimaging studies have implicated micro- and macrostructural abnormalities in white matter in the risk and progression of AD, suggesting that in addition to the neuronal pathology characteristic of the disease, white matter degeneration and demyelination may be also important pathophysiological features. Here we review the evidence for white matter abnormalities in AD with a focus on myelin and oligodendrocytes, the only source of myelination in the central nervous system, and discuss the relationship between white matter changes and the hallmarks of Alzheimer's disease. We review several mechanisms such as ischemia, oxidative stress, excitotoxicity, iron overload, Aβ toxicity and tauopathy, which could affect oligodendrocytes. We conclude that white matter abnormalities, and in particular myelin and oligodendrocytes, could be mechanistically important in AD pathology and could be potential treatment targets.
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Oligodendrocytes are the most probable cellular substrate of myelin abnormalities.
“Being the only cell type to produce and maintain myelination in the human central nervous system, OL is the most probable cellular substrate of myelin abnormalities (Nasrabady et al. 2018).”
From Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte‐derived lipid transport (2023) · cites this paper as Nasrabady et al. 2018
White matter lesions promote the formation of neurofibrillary tangles.
“WMLs promote the formation of NFTs [45].”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [45]
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“…vessel cerebrovascular disease, an expanding body of literature suggests that the emergence of WM abnormalities is also secondary to Alzheimer ’ s disease (AD) pathologic changes (Nasrabady et al., 2018; Araque Caballero et al., 2018; Dean et al., 2017; Strain et al., 2018; Jacobs et al., 2018).”
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- Authors
- Nasrabady, S. E., Rizvi, B., Goldman, J. E., & Brickman, A. M.
- Affiliations
- Columbia University (US)
- Corresponding author
- Nasrabady, Sara E.
- Venue
- Acta Neuropathologica Communications
- Published
- 2018-03-02
- Volume
- 6
- Issue
- 1
- Pages
- 22-22
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC5834839
- OpenAlex
- W2793877399
- Cited by
- 723
- References
- 86
- Citations by year
- 2026: 82 · 2025: 112 · 2024: 103 · 2023: 118 · 2022: 93 · 2021: 101 · 2020: 73 · 2019: 34 · 2018: 6 · 2012: 1
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Columbia Academic Commons (Columbia University)
- Funders
- NIH T32 grant (MH 20004-19)
- National Institutes of Health (P50 AG008702)
- Alzheimer's Association
- The Taub Institute for Research on Alzheimer's Disease and the Aging Brain
- The Mary E. Groff Charitable Trust
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, white matter, myelin, oligodendrocytes, demyelination, white matter degeneration, amyloid-beta, tauopathy, oxidative stress, excitotoxicity, iron overload, ischemia, neurofibrillary tangles, amyloid plaques, treatment goals
- MeSH terms
- Alzheimer Disease, Animals, Humans, Myelin Sheath, White Matter
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