The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index.
Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides
Abstract
We have previously shown that apolipoprotein E (Apoe) promotes the formation of amyloid in brain and that astrocyte-specific expression of APOE markedly affects the deposition of amyloid-beta peptides (Abeta) in a mouse model of Alzheimer disease. Given the capacity of astrocytes to degrade Abeta, we investigated the potential role of Apoe in this astrocyte-mediated degradation. In contrast to cultured adult wild-type mouse astrocytes, adult Apoe(-/-) astrocytes do not degrade Abeta present in Abeta plaque-bearing brain sections in vitro. Coincubation with antibodies to either Apoe or Abeta, or with RAP, an antagonist of the low-density lipoprotein receptor family, effectively blocks Abeta degradation by astrocytes. Phase-contrast and confocal microscopy show that Apoe(-/-) astrocytes do not respond to or internalize Abeta deposits to the same extent as do wild-type astrocytes. Thus, Apoe seems to be important in the degradation and clearance of deposited Abeta species by astrocytes, a process that may be impaired in Alzheimer disease.
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In the citing paper
“Moreover, this plaque-degrading activity in astrocytes was subsequently found to be dependent on apolipoprotein E (apoE) expression (42).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [42]
In the citing paper
“In a mouse model of amyloid deposition, ApoE has been reported to promote the localization of astrocytes to plaques (19).”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [19]
In the citing paper
“Several studies have shown that astrocytes are capable of taking up amyloid peptides (Funato et al., 1998; Matsunaga et al., 2003; Nagele et al., 2003; Lasagna-Reeves and Kayed, 2011), and in vitro this ability was restricted to adult astrocytes (al-Ali and al-Hussain, 1996; Wyss-Coray et al., 2003; Koistinaho et al., 2004; Pihlaja et al., 2008).”
From Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease (2012) · cites this paper as Koistinaho et al., 2004
In the citing paper
“endogenous CNS-derived apoE-containing lipoprotein particles bind to A and promote its clearance and degradation (DeMattos et al., 2004;Koistinaho et al., 2004;Manelli et al., 2004;Stratman et al., 2005;Trommer et al., 2005)”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Koistinaho et al., 2004
In the citing paper
“It has been demonstrated that only mature astrocytes from adult mice, but not neonatal astrocytes, are capable of phagocytosing Aβ plaques (Wyss-Coray et al., 2003;Koistinaho et al., 2004).”
From Cell Adhesion Molecule Protocadherin-γC5 Ameliorates Aβ Plaque Pathogenesis by Modulating Astrocyte Function in Alzheimer's Disease (2025) · cites this paper as Koistinaho et al., 2004
In the citing paper
“It has been reported that the phagocytosis ability of astrocytes is dependent on mouse age.Only mature astrocytes cultured from adult, but not neonatal, mice was able to phagocytose and degrade Aβ, reducing Aβ plaques (Wyss-Coray et al., 2003;Koistinaho et al., 2004).”
From Cell Adhesion Molecule Protocadherin-γC5 Ameliorates Aβ Plaque Pathogenesis by Modulating Astrocyte Function in Alzheimer's Disease (2025) · cites this paper as Koistinaho et al., 2004
In the citing paper
“reactive astrocytes have been reported to phagocytose and degrade Aβ, reducing Aβ plaque burden in the brain (Wyss-Coray et al., 2003;Koistinaho et al., 2004;Kraft et al., 2013;Gomez-Arboledas et al., 2018;Preman et al., 2021)”
From Cell Adhesion Molecule Protocadherin-γC5 Ameliorates Aβ Plaque Pathogenesis by Modulating Astrocyte Function in Alzheimer's Disease (2025) · cites this paper as Koistinaho et al., 2004
In the citing paper
“Two in vitro studies have also demonstrated that apoE can facilitate the cellular degradation of Aβ (Jiang et al., 2008; Koistinaho et al., 2004).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Koistinaho et al., 2004
In the citing paper
“One common hypothesis states that APOE sequesters soluble Aβ in the extracellular space resulting in cellular uptake and catabolism of this neurotoxic peptide. This hypothesis is supported by many in vitro studies (Koistinaho et al., 2004; Morikawa et al., 2005; Jiang et al., 2008).”
From The Pro-Neurotrophin Receptor Sortilin Is a Major Neuronal Apolipoprotein E Receptor for Catabolism of Amyloid-β Peptide in the Brain (2013) · cites this paper as Koistinaho et al., 2004
In the citing paper
“In the brain, endocytic pathways in glia cells (likely the LDL receptor) and in neurons are implicated in cellular catabolism of APOE/Aβ complexes (Koistinaho et al., 2004; Jiang et al., 2008; Holtzman et al., 2012).”
From The Pro-Neurotrophin Receptor Sortilin Is a Major Neuronal Apolipoprotein E Receptor for Catabolism of Amyloid-β Peptide in the Brain (2013) · cites this paper as Koistinaho et al., 2004
In the citing paper
“In the context of neurodegeneration, astrocytes take up aggregate-prone MAPT/tau, amyloid beta (Aβ) and SNCA (synuclein alpha), and degrade these proteins through autophagy [407–412].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [407]
Citations
Cites
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Measurement of co‐localization of objects in dual‐colour confocal images
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Activation of microglial cells by β-amyloid protein and interferon-γ
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Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions
William Rebeck, G., Reiter, J. S., Strickland, D. K., & Hyman, B. T. (1993) · Neuron · doi:10.1016/0896-6273(93)90070-8 · Cited by 1,107
Adult mouse astrocytes degrade amyloid-β in vitro and in situ
Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., & Husemann, J. (2003) · Nature Medicine · doi:10.1038/nm838 · Cited by 909
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
Self-citationTGF-β1 promotes microglial amyloid-β clearance and reduces plaque burden in transgenic mice
Wyss-Coray, T., Lin, C., Yan, F., Yu, G.-Q., Rohde, M., McConlogue, L., Masliah, E., & Mucke, L. (2001) · Nature Medicine · doi:10.1038/87945 · Cited by 587
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Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
Astrocytes: Biology and pathology
Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969
Molecular dissection of reactive astrogliosis and glial scar formation
Sofroniew, M. V. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.08.002 · Cited by 2,594
Metadata
- Authors
- Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K. R., & Paul, S. M.
- Affiliations
- Eli Lilly (United States) (US)
- Corresponding author
- Paul, Steven M
- Venue
- Nature Medicine
- Published
- 2004-06-13
- Volume
- 10
- Issue
- 7
- Pages
- 719-726
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2171311951
- Cited by
- 571
- References
- 40
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 15 · 2023: 20 · 2022: 29 · 2021: 23 · 2020: 34 · 2019: 31 · 2018: 26 · 2017: 29 · 2016: 32 · 2015: 29 · 2014: 36 · 2013: 30 · 2012: 38
- FWCI
- 13.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Suomen Kulttuurirahasto
- Saastamoisen säätiö
- 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
- apolipoprotein E, amyloid-beta, astrocytes, amyloid beta degradation, Alzheimer's disease, amyloid plaques, rap, low-density lipoprotein receptor family, ApoE-deficient mice
- MeSH terms
- Animals, Apolipoproteins E, Astrocytes, Cell Aggregation, Cell Survival, Cells, Cultured, Mice, Inbred C57BL, Amyloid beta-Peptides, Low Density Lipoprotein Receptor-Related Protein-1, Mice
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