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Increased Susceptibility to Amyloid-β-Induced Neurotoxicity in Mice Lacking the Low-Density Lipoprotein Receptor
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Experimental models of hypercholesterolemia reveal that early pathological events such as neuroinflammation and BBB dysfunction precede brain impairment.
“This link is supported by experimental models of hypercholesterolemia, which reveal that early pathological events such as neuroinflammation and blood–brain barrier (BBB) dysfunction precede brain impairment (de Oliveira et al. 2014; de Oliveira, Engel, de Paula, Dos Santos, et al. 2020; de Oliveira, Engel, de Paula, Melo, et al. 2020; Moreira et al. 2012; Paul and Borah 2017; Rodrigues et al. 202”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as de Oliveira et al. 2014
Astrogliosis, classically characterized by increased GFAP immunoreactivity, is a prominent feature of hypercholesterolemic animal models and frequently co-localizes with regions of BBB disruption.
“Consistent with this role, astrogliosis, classically characterized by increased glial fibrillary acid protein (GFAP) immunoreactivity, is a prominent feature of hypercholesterolemic animal models and frequently co‐localizes with regions of BBB disruption (Ramírez et al. 2011; de Oliveira et al. 2014; de Oliveira, Engel, de Paula, Dos Santos, et al. 2020).”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as de Oliveira et al. 2014
Prior studies have shown that LDLr−/− mice already exhibit BBB dysfunction, neuroinflammation, astrogliosis, oxidative stress, and memory deficits at the young adult stage.
“Notably, our prior studies have shown that LDLr−/− mice already exhibit BBB dysfunction, neuroinflammation, astrogliosis, oxidative stress, and memory deficits at this young adult stage (de Oliveira et al. 2014; de Oliveira, Engel, de Paula, Dos Santos, et al. 2020; de Oliveira, Engel, de Paula, Melo, et al. 2020).”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as de Oliveira et al. 2014
Previous studies from the research group have demonstrated elevated GFAP immunoreactivity in young LDLr−/− mice compared with wild-type controls, indicating early biochemical signatures of astrocyte activation.
“Previous studies from our research group have demonstrated elevated GFAP immunoreactivity in young LDLr−/− mice compared with wild‐type controls (de Oliveira et al. 2014; de Oliveira, Engel, de Paula, Dos Santos, et al. 2020), indicating early biochemical signatures of astrocyte activation.”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as de Oliveira et al. 2014
We previously observed an increased immunoreactivity of AQP4 in the hippocampus of LDLr−/− mice.
“We previously observed an increased immunoreactivity of this protein in the hippocampus of LDLr−/− mice (de Oliveira et al. 2014).”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as de Oliveira et al. 2014
Previous studies have reported increased astrocyte density in the hippocampus of LDLr−/− mice.
“Previous studies have reported increased astrocyte density in the hippocampus of LDLr−/− mice (de Oliveira et al. 2014; de Oliveira, Engel, de Paula, Dos Santos, et al. 2020) and have identified age‐dependent heterogeneity in astrocytic reactivity profiles (Clarke et al. 2018; Lee et al. 2022).”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as de Oliveira et al. 2014
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Cites
Astrocytes: Biology and pathology
Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196
Alzheimer’s disease: Clinical trials and drug development
Mangialasche, F., Solomon, A., Winblad, B., Mecocci, P., & Kivipelto, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70119-8 · Cited by 1,217
Inflammation in Alzheimer Disease--A Brief Review of the Basic Science and Clinical Literature
Wyss-Coray, T., & Rogers, J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006346 · Cited by 975
Hempel, S. L., Buettner, G. R., O’Malley, Y. Q., Wessels, D. A., & Flaherty, D. M. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00061-1 · Cited by 740
Cholesterol metabolism in neurons and astrocytes
Pfrieger, F. W., & Ungerer, N. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2011.06.002 · Cited by 500
Lipoprotein receptors in the nervous system
Herz, J., & Bock, H. H. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135342 · Cited by 457
Kim, J., Castellano, J. M., Jiang, H., Basak, J. M., Parsadanian, M., Pham, V., Mason, S. M., Paul, S. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.013 · Cited by 274 · cited 1×
“…itedgeneticabnormalitiesthatdirectlyorindi-rectlyaffect LDLr function, implying an ineffective reported that lack of LDLr increases A (cid:1) deposition reduction in A (cid:1) load was observed in A (cid:1) PP/PS1 transgenic mice overexpressing LDLr in the brain [38].”
Immune reactive cells in senile plaques and cognitive decline in Alzheimer’s disease
Vehmas, A. K., Kawas, C. H., Stewart, W. F., & Troncoso, J. C. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00090-8 · Cited by 230
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Functional Roles of the Interaction of APP and Lipoprotein Receptors
Pohlkamp, T., Wasser, C. R., & Herz, J. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00054 · Cited by 92
Do, H. T., Bruelle, C., Pham, D. D., Jauhiainen, M., Eriksson, O., Korhonen, L. T., & Lindholm, D. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13397 · Cited by 37
de Oliveira, J., Engel, D. F., de Paula, G. C., Melo, H. M., Lopes, S. C., Ribeiro, C. T., Delanogare, E., Moreira, J. C. F., Gelain, D. P., Prediger, R. D., et al. (2020) · Journal of Alzheimer’s Disease · doi:10.3233/jad-190742 · Cited by 31
Self-citationBaumart, G. J., Rodrigues, M. S., Sholl, J. N., de Sousa, A. C., Weber, A. F., Costa‐Beber, L. C., Farias, H. R., Costa, M. V., Peres, A. M., de Camargo, P. R., et al. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70403 · Cited by 2
de Oliveira, J., de Bem, A. F., & Moreira, E. L. G. (2014) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12309
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Metadata
- Authors
- de Oliveira, J., Moreira, E. L. G., dos Santos, D. B., Piermartiri, T. C., Dutra, R. C., Pinton, S., Tasca, C. I., Farina, M., Prediger, R. D. S., & de Bem, A. F.
- Affiliations
- Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
- Universidade Federal do Pampa, Uruguaiana, RS, Brazil
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2014-06-04
- Volume
- 41
- Issue
- 1
- Pages
- 43-60
- ISSN
- 1875-8908
- 1387-2877
- Cited by
- 62
- References
- 8
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