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Is Alzheimer’s a disease of the white matter?
Abstract
PURPOSE OF REVIEW: Alzheimer's disease has long been primarily considered a disease of gray matter. However, convergent evidence has suggested that white matter abnormalities are also important components of Alzheimer's disease. We undertook a review of the recent findings of Alzheimer's disease related white matter aberrations identified in patients with Alzheimer's disease and using in-vitro and in-vivo models, and discuss the potential causes of white matter damage in Alzheimer's disease. In doing so, we aim to provide a renewed insight into white matter changes in Alzheimer's disease and related dementias. RECENT FINDINGS: Neuroimaging studies have found that patients with preclinical Alzheimer's disease have widespread white matter abnormalities at a stage similar to those reported in Alzheimer's disease, whereas gray matter structures were relatively intact. In addition, demyelination of the white matter is reported to occur prior to the presence of amyloid-β plaques and neurofibrillary tangles in the presymptomatic stages of Alzheimer's disease. Furthermore, in a mouse model of Alzheimer's disease, axonal disease due to impaired axonal transport was shown to precede and drive downstream production and aggregation of amyloid β peptides. SUMMARY: White matter abnormalities not only represent an early neuropathological event in Alzheimer's disease but may also play an important role in the pathogenesis and diagnosis of Alzheimer's disease.
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“Thus, increased amyloid pathology may contribute to microvascular damage leading to white matter degeneration (for review see Sachdev et al., 2013).”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Sachdev et al., 2013
In the citing paper
“white matter abnormalities have been widely reported in the brains of incipient and mildly afflicted individuals (Sachdev et al., 2013).”
From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Sachdev et al., 2013
In the citing paper
“In aggregate, these studies point to WM abnormalities in AD, which may play a key role in early pathogenesis and diagnosis (Sachdev et al., 2013).”
From Diffusion MRI Indices and Their Relation to Cognitive Impairment in Brain Aging: The Updated Multi-protocol Approach in ADNI3 (2019) · cites this paper as Sachdev et al., 2013
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Metadata
- Authors
- Sachdev, P. S., Zhuang, L., Braidy, N., & Wen, W.
- Affiliations
- UNSW Sydney (AU)
- Corresponding author
- Sachdev, Perminder S.
- Venue
- Current Opinion in Psychiatry
- Published
- 2013-05
- Volume
- 26
- Issue
- 3
- Pages
- 244-251
- ISSN
- 0951-7367 (ISSN-L)
- OpenAlex
- W2086015438
- Cited by
- 137
- References
- 101
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 14 · 2023: 16 · 2022: 12 · 2021: 16 · 2020: 11 · 2019: 9 · 2018: 13 · 2017: 9 · 2016: 10 · 2015: 5 · 2014: 8 · 2013: 2
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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 abnormalities, demyelination, amyloid-beta, preclinical Alzheimer's disease, neurofibrillary tangles, mouse models of Alzheimer's disease, dementia pathogenesis, early diagnosis
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Humans, Mice, Leukoencephalopathies, Neuroimaging
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