Changes in Chromatin Structure Associated with Alzheimer’s Disease
Abstract
The enzyme micrococcal nuclease was used to examine the accessibility of chromatin extracted from brains of 13 patients with senile and presenile dementia of the Alzheimer type. Compared with chromatin extracted from brains of 8 patients without neurological signs or brain pathology and brains of 7 patients with nonAlzheimer dementia, Alzheimer chromatin was less accessible to this enzyme. Reduced accessibility was reflected by a reduced yield of mononucleosomes in comparison with dinucleosomes and larger oligomers. Both neuronal and glial chromatin were found to be similarly affected. The reduced yield of mononucleosomes from Alzheimer chromatin is not due to their increased breakdown, but is probably related to protein associated with the internucleosomal linker region that retards nuclease action. Dinucleosomes isolated from control and Alzheimer nuclease digests were examined for their protein complement. Three perchloric acid-soluble proteins situated in the histone H1 region of sodium dodecyl sulfate (SDS) gels were present in elevated levels in Alzheimer dinucleosomes. These results represent the first example of altered chromosomal proteins associated with a diseased state of the brain.
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Chromatin accessibility has been shown to be disrupted in the AD brain.
“Chromatin accessibility has also been shown to be disrupted in the AD brain”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [44]
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- Authors
- Lewis, P. N., Lukiw, W. J., De Boni, U., & Crapper McLachlan, D. R.
- Affiliations
- University of Toronto (CA)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1981-11
- Volume
- 37
- Issue
- 5
- Pages
- 1193-1202
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2032531559
- Cited by
- 78
- References
- 32
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2015: 3 · 2014: 1
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, chromatin structure, chromatin accessibility, staphylococcal nuclease, dinucleosome, mononucleosomes, histone H1, senile dementia, early-onset dementia
- MeSH terms
- Adult, Aged, Alzheimer Disease, Base Composition, Brain, Chromatin, Dementia, DNA, Humans, Micrococcal Nuclease, Middle Aged, Nucleosomes
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