Alzheimer's disease: An acquired neurodegenerative laminopathy
Open accessAbstract
The nucleus is typically depicted as a sphere encircled by a smooth surface of nuclear envelope. For most cell types, this depiction is accurate. In other cell types and in some pathological conditions, however, the smooth nuclear exterior is interrupted by tubular invaginations of the nuclear envelope, often referred to as a "nucleoplasmic reticulum," into the deep nuclear interior. We have recently reported a significant expansion of the nucleoplasmic reticulum in postmortem human Alzheimer's disease brain tissue. We found that dysfunction of the nucleoskeleton, a lamin-rich meshwork that coats the inner nuclear membrane and associated invaginations, is causal for Alzheimer's disease-related neurodegeneration in vivo. Additionally, we demonstrated that proper function of the nucleoskeleton is required for survival of adult neurons and maintaining genomic architecture. Here, we elaborate on the significance of these findings in regard to pathological states and physiological aging, and discuss cellular causes and consequences of nuclear envelope invagination.
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AD has been explicitly referred to as an acquired neurodegenerative laminopathy, and lamin dysfunction has been shown to drive tau-mediated neurodegeneration.
“Indeed, AD has been explicitly referred to as an acquired neurodegenerative laminopathy [41], and lamin dysfunction has been shown to drive tau-mediated neurodegeneration [42].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [41]
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- Authors
- Frost, B.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Frost, Bess
- ORCID
- Frost, Bess
- Venue
- Nucleus
- Publisher
- Informa UK Limited
- Published
- 2016-05-03
- Volume
- 7
- Issue
- 3
- Pages
- 275-283
- ISSN
- 1949-1034 (ISSN-L)
- 1949-1042
- PMC
- PMC4991240
- OpenAlex
- W2352506248
- Cited by
- 74
- References
- 68
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 2 · 2023: 10 · 2022: 7 · 2021: 15 · 2020: 9 · 2019: 6 · 2018: 8 · 2017: 4
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleus (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG057896)
- National Institute of Neurological Disorders and Stroke (R00NS088429)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Alzheimer's disease, laminopathies, nucleoskeleton, nuclear envelope invaginations, nuclear lamina, neurodegeneration, genome organization, aging, postmortem brain
- MeSH terms
- Alzheimer Disease, Animals, Humans, Mutation, Neurons, Tauopathies, Nuclear Lamina, Lamin Type B
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