The DOI matches its Crossref record; 47 of the 49 references it cites were found in a registry or an index.
Activation of the Amyloid Cascade in Apolipoprotein E4 Transgenic Mice Induces Lysosomal Activation and Neurodegeneration Resulting in Marked Cognitive Deficits
Open accessAbstract
The allele E4 of apolipoprotein E (apoE4), the most prevalent genetic risk factor for Alzheimer's disease, is associated histopathologically with elevated levels of brain amyloid. This led to the suggestion that the pathological effects of apoE4 are mediated by cross-talk interactions with amyloid β peptide (Aβ), which accentuate the pathological effects of the amyloid cascade. The mechanisms underlying the Aβ-mediated pathological effects of apoE4 are unknown. We have shown recently that inhibition of the Aβ-degrading enzyme neprilysin in brains of wild-type apoE3 and apoE4 mice results in rapid and similar elevations in their total brain Aβ levels. However, the nucleation and aggregation of Aβ in these mice were markedly affected by the apoE genotype and were specifically enhanced in the apoE4 mice. We presently used the neprilysin inhibition paradigm to analyze the neuropathological and cognitive effects that are induced by apoE4 after activation of the amyloid cascade. This revealed that apoE4 stimulates isoform specifically the degeneration of hippocampal CA1 neurons and of entorhinal and septal neurons, which is accompanied by the accumulation of intracellular Aβ and apoE and with lysosomal activation. Furthermore, these neuropathological effects are associated isoform specifically with the occurrence of pronounced cognitive deficits in the ApoE4 mice. These findings provide the first in vivo evidence regarding the cellular mechanisms underlying the pathological cross talk between apoE4 and Aβ, as well as a novel model system of neurodegeneration in vivo that is uniquely suitable for studying the early stages of the amyloid cascade and the effects thereon of apoE4.
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“Several recent studies provided evidence to support increased content of Ab oligomers in the extracellular space in brains of patients with AD, expressing the human ApoE4 isoform, 37,38 and intraneuronally in mice expressing human ApoE4 isoform after inhibition of Ab-degrading enzyme neprilysin.39”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [39]
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“As shown in another model involving inhibition of the Ab-degrading enzyme neprilysin, intraneuronal oligomerization and accumulation of Ab occurred more readily in mice that expressed the ApoE4 isoform than the ApoE3 isoform.39”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [39]
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769
RetractedThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · cited 1×
“, 1995; Goedert and Spillantini, 2006; Masters and Beyreuther, 2006), and the allele E4 of apolipoprotein E (apoE4), which is the most prevalent genetic risk factor for AD (Corder et al., 1993; Saunders et al., 1993; Roses, 2006).”
BackgroundTriple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786
mouse brain in stereotaxic coordinates
Franklin, K. B. J., & Paxinos, G. (1997) · Cited by 3,258
A Century of Alzheimer's Disease
Goedert, M., & Spillantini, M. G. (2006) · Science · doi:10.1126/science.1132814 · Cited by 2,153 · cited 1×
“These include amyloid peptide (A ) and hyperphosphorylated tau, which are the major constituents of senile plaques and neurofibrilary tangles, respectively (Alzheimer et al., 1995; Goedert and Spillantini, 2006; Masters and Beyreuther, 2006), and the allele E4 of apolipoprotein E (apoE4), which is the most prevalent g…”
BackgroundIntracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942
Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B. J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9649 · Cited by 1,525
An english translation of alzheimer’s 1907 paper, “über eine eigenartige erkankung der hirnrinde”
Stelzmann, R. A., Norman Schnitzlein, H., & Reed Murtagh, F. (1995) · Clinical Anatomy · doi:10.1002/ca.980080612 · Cited by 1,455
Research works printed but not linked: 2
- Geula C Mesulam MM (1999) in Alzheimer disease, Cholinergic system in Alzheimer disease, eds Terry RD Katzman R Bick KL Sisodia SS (Lippincott, Williams, and Wilkins, Philadelphia), Ed 2, p 457.
- Hof PR Morrison JH (1999) in Alzheimer Disease, The cellular basis of cortical disconnection in Alzheimer disease and related dementing conditions, eds Terry RD Katzman R Bick KL Sisodia SS (Lippincott, Williams, and Wilkins, Philadelphia), Ed 2, p 457.
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Items 101–101 of 101
Metadata
- Authors
- Belinson, H., Lev, D., Masliah, E., & Michaelson, D. M.
- Affiliations
- Tel Aviv University (IL)
- University of California San Diego (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-04-30
- Volume
- 28
- Issue
- 18
- Pages
- 4690-4701
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3844816
- OpenAlex
- W2085235587
- Cited by
- 101
- References
- 49
- Citations by year
- 2025: 3 · 2024: 7 · 2023: 1 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 10 · 2015: 3 · 2014: 3 · 2013: 9 · 2012: 10
- FWCI
- 5.66
- 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
- National Institutes of Health (AG‐022074, AG10435)
- National Institute on Aging (P01AG010435, AG022074, P01AG022074, AG48440, AG10435)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- APOE ε4, amyloid hypothesis, amyloid-beta, neprilysin inhibition, lysosomal activation, neurodegeneration, cognitive impairment, CA1 pyramidal neurons, entorhinal cortex, septal neurons, amyloid-beta aggregation, Alzheimer's disease, transgenic mice
- MeSH terms
- Analysis of Variance, Animals, Cognition Disorders, Disease Models, Animal, Exploratory Behavior, Hippocampus, Learning, Lysosomes, Mice, Inbred C57BL, Mice, Transgenic, Neuropsychological Tests, Synapses, Water Deprivation, Neprilysin, Amyloid beta-Peptides, Drug Delivery Systems, Neurodegenerative Diseases, Microscopy, Electron, Transmission, Mice, Apolipoprotein E3, Apolipoprotein E4
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