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White matter changes in Alzheimer's disease: a focus on myelin and oligodendrocytes
Sara E Nasrabady1, Batool Rizvi2, James E Goldman3,2
1Department of Psychiatry, Columbia University, New York, NY, USA. se2351@columbia.edu.
Abstract:
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.
Insights
Alzheimer's disease involves white matter damage, particularly to myelin and oligodendrocytes. These changes are linked to disease hallmarks and may offer new therapeutic targets.
Area of Science:
- Neuroscience
- Neuropathology
- Neuroimaging
Background:
- Alzheimer's disease (AD) traditionally focuses on grey matter pathology (amyloid plaques, neurofibrillary tangles).
- Emerging evidence highlights white matter abnormalities in AD risk and progression.
- White matter degeneration and demyelination are increasingly recognized as key pathophysiological features.
Purpose of the Study:
- To review evidence of white matter abnormalities in Alzheimer's disease.
- To focus on the role of myelin and oligodendrocytes in AD.
- To discuss mechanisms linking white matter changes to AD hallmarks and potential therapeutic targets.
Main Methods:
- Review of neuroimaging studies implicating white matter changes in AD.
- Analysis of pathological evidence focusing on myelin and oligodendrocytes.
- Synthesis of proposed mechanisms affecting oligodendrocytes in AD.
Main Results:
- Neuroimaging studies consistently show micro- and macrostructural white matter abnormalities in AD.
- Oligodendrocytes, responsible for myelination, are implicated in AD pathogenesis.
- Multiple mechanisms (ischemia, oxidative stress, Aβ toxicity, tauopathy) can impact oligodendrocytes.
Conclusions:
- White matter abnormalities, especially involving myelin and oligodendrocytes, are mechanistically important in Alzheimer's disease.
- These white matter changes are closely related to established AD hallmarks.
- Oligodendrocytes and myelin represent promising targets for future AD therapies.