Apolipoprotein E co-localizes with newly formed amyloid β-protein (Aβ) deposits lacking immunoreactivity against N-terminal epitopes of Aβ in a genotype-dependent manner
Abstract
Different types of amyloid beta-protein (Abeta)-containing plaques occur in brains of Alzheimer's disease (AD) patients. Diffuse plaques seen during early stages of AD differ from neuritic plaques in later stages both with respect to the length of the Abeta peptides and the presence of other proteins, e.g., apolipoprotein-E (apoE). Since apoE is involved in Abeta transport and clearance, and the epsilon4-allele of the apolipoprotein-E gene (APOE) is a major risk factor for sporadic AD, it is plausible to speculate that apoE plays a pathophysiological role in the initiation of Abeta deposition. To address the issue of whether binding of apoE to Abeta is involved in initial Abeta deposition, we studied the human medial temporal lobe of 60 autopsy cases encompassing the full spectrum of AD-related pathology. In temporal lobe regions, which become involved for the first time at a given stage of beta-amyloidosis, all plaques represent newly formed plaques, and these were studied with immunohistochemical methods. ApoE was present in 36 cases, and was frequently co-localized with newly formed Abeta deposits detectable with anti-Abeta(42) but not with antibodies raised against N-terminal epitopes of Abeta. In 10 additional cases, immunoreactivity against apoE was completely lacking in newly formed plaques, which, at the same time, displayed immunoreactivity against N-terminal epitopes of Abeta. The failure of N-terminal epitopes of Abeta to co-localize with apoE in newly formed plaqu…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ApoE colocalizes with newly formed Aβ deposits.
“Previous work has shown that apoE colocalizes with newly formed A deposits and that apoE4 carriers show more apoE containing newly formed plaques than individuals with other apoE genotypes, suggesting the involvement of apoE in the initiation of plaque formation (Thal et al., 2005).”
From Anti-ApoE Antibody Given after Plaque Onset Decreases Aβ Accumulation and Improves Brain Function in a Mouse Model of Aβ Amyloidosis (2014) · cites this paper as Thal et al., 2005
ApoE4 carriers show more apoE containing newly formed plaques than individuals with other apoE genotypes.
“Previous work has shown that apoE colocalizes with newly formed A deposits and that apoE4 carriers show more apoE containing newly formed plaques than individuals with other apoE genotypes, suggesting the involvement of apoE in the initiation of plaque formation (Thal et al., 2005).”
From Anti-ApoE Antibody Given after Plaque Onset Decreases Aβ Accumulation and Improves Brain Function in a Mouse Model of Aβ Amyloidosis (2014) · cites this paper as Thal et al., 2005
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Self-citationIwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline
Näslund, J. (2000) · JAMA · doi:10.1001/jama.283.12.1571 · Cited by 1,268 · see citing works
Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition
Bales, K. R., Verina, T., Dodel, R. C., Du, Y., Altstiel, L., Bender, M., Hyslop, P., Johnstone, E. M., Little, S. P., Cummins, D. J., et al. (1997) · Nature Genetics · doi:10.1038/ng1197-263 · Cited by 830 · see citing works
Lemere, C. A., Blusztajn, J. K., Yamaguchi, H., Wisniewski, T., Saido, T. C., & Selkoe, D. J. (1996) · Neurobiology of Disease · doi:10.1006/nbdi.1996.0003 · Cited by 584 · see citing works
Self-citationApolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1058 · Cited by 571 · see citing works
Kang, D. E., Pietrzik, C. U., Baum, L., Chevallier, N., Merriam, D. E., Kounnas, M. Z., Wagner, S. L., Troncoso, J. C., Kawas, C. H., Katzman, R., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11013 · Cited by 354 · see citing works
Amino- and carboxyl-terminal heterogeneity of β-amyloid peptides deposited in human brain
Saido, T. C., Yamao-Harigaya, W., Iwatsubo, T., & Kawashima, S. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12970-0 · Cited by 270 · see citing works
Self-citationSadowski, M., Pankiewicz, J., Scholtzova, H., Ripellino, J. A., Li, Y., Schmidt, S. D., Mathews, P. M., Fryer, J. D., Holtzman, D. M., Sigurdsson, E. M., et al. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63355-x · Cited by 154 · see citing works
Thal, D. R., Schultz, C., Dehghani, F., Yamaguchi, H., Braak, H., & Braak, E. (2000) · Acta Neuropathologica · doi:10.1007/s004010000242 · Cited by 136 · see citing works
Self-citationWisniewski, H. M., Sadowski, M., Jakubowska-Sadowswka, K., Tarnawski, M., & Wegiel, J. (1998) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199807000-00004 · Cited by 71 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Classification and basic pathology of Alzheimer disease
Duyckaerts, C., Delatour, B., & Potier, M.-C. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0532-1 · Cited by 1,031 · see citing works
ApoE4 Accelerates Early Seeding of Amyloid Pathology
Liu, C.-C., Zhao, N., Fu, Y., Wang, N., Linares, C., Tsai, C.-W., & Bu, G. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.013 · Cited by 451 · see citing works
Review: sporadic cerebral amyloid angiopathy
Attems, J., Jellinger, K., Thal, D. R., & Van Nostrand, W. (2011) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2010.01137.x · Cited by 371 · see citing works
Self-citationThe Development of Amyloid β Protein Deposits in the Aged Brain
Thal, D. R., Capetillo-Zarate, E., Del Tredici, K., & Braak, H. (2006) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2006.6.re1 · Cited by 234 · see citing works
Self-citationApolipoprotein E and Alzheimer’s disease: Findings, hypotheses, and potential mechanisms
Koutsodendris, N., Nelson, M. R., Rao, A., & Huang, Y. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-030421-112756 · Cited by 231 · see citing works
Thal, D. R., Griffin, W. S. T., & Braak, H. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00411.x · Cited by 134 · see citing works
Self-citationLiao, F., Hori, Y., Hudry, E., Bauer, A. Q., Jiang, H., Mahan, T. E., Lefton, K. B., Zhang, T. J., Dearborn, J. T., Kim, J., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0646-14.2014 · Cited by 128 · see citing works
“Previous work has shown that apoE colocalizes with newly formed A deposits and that apoE4 carriers show more apoE containing newly formed plaques than individuals with other apoE genotypes, suggesting the involvement of apoE in the initiation of plaque formation (Thal et al., 2005).”
BackgroundExtracellular Proteolysis of Apolipoprotein E (apoE) by Secreted Serine Neuronal Protease
Tamboli, I. Y., Heo, D., & Rebeck, G. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093120 · Cited by 35 · see citing works
Gal, J., Katsumata, Y., Zhu, H., Srinivasan, S., Chen, J., Johnson, L. A., Wang, W.-X., Golden, L. R., Wilcock, D. M., Jicha, G. A., et al. (2022) · The American Journal of Pathology · doi:10.1016/j.ajpath.2021.11.013 · Cited by 17 · see citing works
- Authors
- Thal, D. R., Capetillo-Zarate, E., Schultz, C., Rüb, U., Saido, T. C., Yamaguchi, H., Haass, C., Griffin, W. S. T., Del Tredici, K., Braak, H., & Ghebremedhin, E.
- Affiliations
- University of Bonn (DE)
- Goethe University Frankfurt (DE)
- RIKEN (JP)
- Gunma University (JP)
- Adolf-Butenandt-Institut für Physiologische Chemie, Physikalische Biochemie und Zellbiologie (DE)
- University of Arkansas Medical Center (US)
- Corresponding author
- Thal, Dietmar Rudolf
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2005-09-30
- Volume
- 110
- Issue
- 5
- Pages
- 459-471
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2019213661
- Cited by
- 50
- References
- 11
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 1 · 2012: 2
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 12411, P01AG012411)
- 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
- apolipoprotein E, amyloid-beta, Alzheimer's disease, amyloid plaques, APOE ε4, N-terminal epitope, medial temporal lobe, diffuse plaques, neuritic plaques, beta-amyloidosis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Amyloidosis, Epitopes, Apolipoproteins E, Female, Genotype, Humans, Immunohistochemistry, Male, Middle Aged, Protein Binding, Risk Factors, Temporal Lobe, Amyloid beta-Peptides, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
