Increased Aβ Peptides and Reduced Cholesterol and Myelin Proteins Characterize White Matter Degeneration in Alzheimer's Disease
Abstract
Relative to the gray matter, there is a paucity of information regarding white matter biochemical alterations and their contribution to Alzheimer's disease (AD). Biochemical analyses of AD white matter combining size-exclusion, normal phase, and gas chromatography, immunoassays, and Western blotting revealed increased quantities of Abeta40 and Abeta42 in AD white matter accompanied by significant decreases in the amounts of myelin basic protein, myelin proteolipid protein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase. In addition, the AD white matter cholesterol levels were significantly decreased while total fatty acid content was increased. In some instances, these white matter biochemical alterations were correlated with patient apolipoprotein E genotype, Braak stage, and gender. Our observations suggest that extensive white matter axonal demyelination underlies Alzheimer's pathology, resulting in loss of capacitance and serious disturbances in nerve conduction, severely damaging brain function. These white matter alterations undoubtedly contribute to AD pathogenesis and may represent the combined effects of neuronal degeneration, microgliosis, oligodendrocyte injury, microcirculatory disease, and interstitial fluid stasis. To accurately assess the success of future therapeutic interventions, it is necessary to have a complete appreciation of the full scope and extent of AD pathology.
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AD pathology in the white matter includes loss of myelin and a decrease in oligodendrocyte proteins.
“AD pathology in the white matter includes the loss of myelin and a decrease in oligodendrocyte proteins [62–68].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [63]
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Self-citation
- Authors
- Roher, A. E., Weiss, N., Kokjohn, T. A., Kuo, Y.-M., Kalback, W., Anthony, J., Watson, D., Luehrs, D. C., Sue, L., Walker, D., Emmerling, M., Goux, W., & Beach, T.
- Affiliations
- The University of Texas at Dallas (US)
- Corresponding author
- Roher, Alex E.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2002-08-22
- Volume
- 41
- Issue
- 37
- Pages
- 11080-11090
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2093707752
- Cited by
- 279
- References
- 1
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 11 · 2023: 14 · 2022: 8 · 2021: 12 · 2020: 13 · 2019: 10 · 2018: 16 · 2017: 8 · 2016: 17 · 2015: 11 · 2014: 18 · 2013: 18 · 2012: 15
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-17490, AG18345, R01AG018345, P01AG017490)
- 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 degeneration, amyloid-beta, Aβ40, amyloid-beta 42, myelin basic protein, myelin proteolipid protein, CNPase, cholesterol, fatty acids, axonal demyelination, APOE genotype, Braak stages, nerve conduction, oligodendrocyte damage
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Cerebral Cortex, Cholesterol, Demyelinating Diseases, Myelin Basic Protein, Fatty Acids, Female, Humans, Male, Middle Aged, Myelin Proteins, Myelin Sheath, Oligodendroglia, Peptide Fragments, Phosphoric Diester Hydrolases, Amyloid beta-Peptides, Myelin Proteolipid Protein, 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
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