Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele
Open accessAbstract
A relationship between the apolipoprotein E (apoE) genotype and the risk to develop Alzheimer’s disease has been established recently. Apolipoprotein synthesis is implicated in developmental processes and in neuronal repair of the adult nervous system. In the present study, we investigated the influence of the apolipoprotein polymorphism on the severity of neuronal degeneration and the extent of plastic dendritic remodeling in Alzheimer’s disease. Changes in length and arborization of dendrites of Golgi-impregnated neurons in the basal nucleus of Meynert, locus coeruleus, raphe magnus nucleus, medial amygdaloid nucleus, pedunculopontine tegmental nucleus, and substantia nigra were analyzed after three-dimensional reconstruction. Patients with either one or two apoE ε4 alleles not only showed a more severe degeneration in all areas investigated than in patients lacking the apoE 4 allele but also revealed significantly less plastic dendritic changes. ApoE ε4 allele copy number, furthermore, had a significant effect on the pattern of dendritic arborization. Moreover, the relationship between the intensity of dendritic growth and both the extent of neuronal degeneration and the stage of the disease seen in patients lacking the apoE ε4 allele was very weak in the presence of one ε4 allele and completely lost in patients homozygous for the ε4 allele. The results provide direct evidence that neuronal reorganization is affected severely in patients with Alzheimer’s disease carrying the apoE ε4 allele. This impairment of neuronal repair might lead to a more rapid functional decompensation, thereby contributing to an earlier onset and more rapid progression of the disease.
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Findings from human subjects are not conclusive in regard to the effects of apoE on neuronal processes.
“In addition, findings from human subjects are not conclusive in regard to the effects of apoE on neuronal processes (Arendt et al., 1997; Schonheit et al., 2007).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Arendt et al., 1997
The Discussion says the study cannot determine whether apoE affects neuronal number and branching in people without Alzheimer’s disease, because no controls carried the ε4 allele. But it also reports a relationship between apoE genotype and neuronal degeneration and dendritic changes in patients with Alzheimer’s disease. The citation therefore supports a specific limitation, not the broader claim that human findings are inconclusive. (LLM, conf=0.84)
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- Authors
- Arendt, T., Schindler, C., Brückner, M. K., Eschrich, K., Bigl, V., Zedlick, D., & Marcova, L.
- Affiliations
- Leipzig University (DE)
- ORCID
- Arendt, Thomas
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1997-01-15
- Volume
- 17
- Issue
- 2
- Pages
- 516-529
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6573225
- OpenAlex
- W2143470402
- Cited by
- 319
- References
- 6
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 10 · 2019: 4 · 2018: 3 · 2017: 8 · 2016: 5 · 2015: 8 · 2014: 10 · 2013: 11 · 2012: 6
- FWCI
- 13.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01KS9504/1)
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, apolipoprotein E, APOE ε4, neuroplasticity, dendritic remodeling, dendritic branching, neurodegeneration, basal ganglia, locus coeruleus, substantia nigra, medial amygdala, pedunculopontine nucleus, disease progression, genetic risk
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Choline O-Acetyltransferase, Dendrites, Female, Genotype, Humans, Male, Nerve Degeneration, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Polymorphism, Genetic, Apolipoprotein E4
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