Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Han, Byung Hee; Zhou, Meng-liang; Johnson, Andrew W.; Singh, Itender; Liao, Fan; Vellimana, Ananth K.; Nelson, James W.; Milner, Eric; Cirrito, John R.; Basak, Jacob; Yoo, Min; Dietrich, Hans H.; Holtzman, David M.; Zipfel, Gregory Joseph

doi:10.1073/pnas.1414930112

Cited by 131Intracerebral and Subarachnoid Hemorrhage ResearchAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Open access

Han, Byung Hee, Zhou, Meng-liang, Johnson, Andrew W., Singh, Itender, Liao, Fan, Vellimana, Ananth K., Nelson, James W., Milner, Eric +6 more·2015·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1414930112PMC PMC4345564

Open this paper in CoChat — free account Open PDF

Abstract

Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid β peptide (Aβ) within walls of cerebral arteries and is an important cause of intracerebral hemorrhage, ischemic stroke, and cognitive dysfunction in elderly patients with and without Alzheimer's Disease (AD). NADPH oxidase-derived oxidative stress plays a key role in soluble Aβ-induced vessel dysfunction, but the mechanisms by which insoluble Aβ in the form of CAA causes cerebrovascular (CV) dysfunction are not clear. Here, we demonstrate evidence that reactive oxygen species (ROS) and, in particular, NADPH oxidase-derived ROS are a key mediator of CAA-induced CV deficits. First, the NADPH oxidase inhibitor, apocynin, and the nonspecific ROS scavenger, tempol, are shown to reduce oxidative stress and improve CV reactivity in aged Tg2576 mice. Second, the observed improvement in CV function is attributed both to a reduction in CAA formation and a decrease in CAA-induced vasomotor impairment. Third, anti-ROS therapy attenuates CAA-related microhemorrhage. A potential mechanism by which ROS contribute to CAA pathogenesis is also identified because apocynin substantially reduces expression levels of ApoE-a factor known to promote CAA formation. In total, these data indicate that ROS are a key contributor to CAA formation, CAA-induced vessel dysfunction, and CAA-related microhemorrhage. Thus, ROS and, in particular, NADPH oxidase-derived ROS are a promising therapeutic target for patients with CAA and AD.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1073/pnas.1414930112

Cites

72 of 72 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Inhibiting NOX with apocynin or genetic deletion of gp91phox in Tg2576 mice overexpressing mutant amyloid precursor protein attenuates cerebral amyloid angiopathy.
“Inhibiting NOX with the naturally occurring compound, apocynin, or genetic deletion of gp91phox in mice (Tg2576) overexpressing mutant amyloid precursor protein (APP), attenuates cerebral amyloid angiopathy (CAA) [115,116].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [115]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
Curcumin Inhibits Formation of Amyloid β Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo
Yang, F., Lim, G. P., Begum, A. N., Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Chen, P. P., Kayed, R., Glabe, C. G., Frautschy, S. A., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m404751200 · Cited by 2,336 · see citing works
Silent Brain Infarcts and the Risk of Dementia and Cognitive Decline
Vermeer, S. E., Prins, N. D., den Heijer, T., Hofman, A., Koudstaal, P. J., & Breteler, M. M. B. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022066 · Cited by 2,313 · see citing works
Cerebral amyloid angiopathy. A critical review.
Vinters, H. V. (1987) · Stroke · doi:10.1161/01.str.18.2.311 · Cited by 1,070 · see citing works
Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease
Kawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00372.2001 · Cited by 1,053 · see citing works
Accelerated Amyloid Deposition in the Brains of Transgenic Mice Coexpressing Mutant Presenilin 1 and Amyloid Precursor Proteins
Borchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023 · see citing works
Aβ42‐driven cerebral amyloidosis in transgenic mice reveals early and robust pathology
Radde, R., Bolmont, T., Kaeser, S. A., Coomaraswamy, J., Lindau, D., Stoltze, L., Calhoun, M. E., Jäggi, F., Wolburg, H., Gengler, S., et al. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400784 · Cited by 986 · see citing works
Apocynin Is Not an Inhibitor of Vascular NADPH Oxidases but an Antioxidant
Heumüller, S., Wind, S., Barbosa-Sicard, E., Schmidt, H. H. H. W., Busse, R., Schröder, K., & Brandes, R. P. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.100214 · Cited by 735 · see citing works
β-Amyloid-mediated vasoactivity and vascular endothelial damage
Thomas, T., Thomas, G., McLendon, C., Sutton, T., & Mullan, M. (1996) · Nature · doi:10.1038/380168a0 · Cited by 703 · see citing works
Curcumin labels amyloid pathology in vivo , disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model
Garcı́a-Alloza, M., Borrelli, L. A., Rozkalne, A., Hyman, B. T., & Bacskai, B. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04613.x · Cited by 663 · see citing works
SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein
Iadecola, C., Zhang, F., Niwa, K., Eckman, C., Turner, S. K., Fischer, E., Younkin, S., Borchelt, D. R., Hsiao, K. K., & Carlson, G. A. (1999) · Nature Neuroscience · doi:10.1038/5715 · Cited by 399 · see citing works
The clinical spectrum of cerebral amyloid angiopathy
Greenberg, S. M., Vonsattel, J. P., Stakes, J. W., Gruber, M., & Finklestein, S. P. (1993) · Neurology · doi:10.1212/wnl.43.10.2073 · Cited by 361 · see citing works
Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease
Hartman, R. E., Shah, A., Fagan, A. M., Schwetye, K. E., Parsadanian, M., Schulman, R. N., Finn, M. B., & Holtzman, D. M. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.08.006 · Cited by 358 · see citing works
Self-citation
Apocynin: Molecular Aptitudes
Stefanska, J., & Pawliczak, R. (2008) · Mediators of Inflammation · doi:10.1155/2008/106507 · Cited by 349 · see citing works
Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein
Park, L., Zhou, P., Pitstick, R., Capone, C., Anrather, J., Norris, E. H., Younkin, L., Younkin, S., Carlson, G., McEwen, B. S., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711568105 · Cited by 332 · see citing works
Cerebral Amyloid Angiopathy: The Vascular Pathology and Complications
MANDYBUR, T. I. (1986) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-198601000-00007 · Cited by 304 · see citing works
Human Apolipoprotein E4 Alters the Amyloid-β 40:42 Ratio and Promotes the Formation of Cerebral Amyloid Angiopathy in an Amyloid Precursor Protein Transgenic Model
Fryer, J. D., Simmons, K., Parsadanian, M., Bales, K. R., Paul, S. M., Sullivan, P. M., & Holtzman, D. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5170-04.2005 · Cited by 278 · see citing works
Self-citation
Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice
Li, F., Calingasan, N. Y., Yu, F., Mauck, W. M., Toidze, M., Almeida, C. G., Takahashi, R. H., Carlson, G. A., Beal, M. F., Lin, M. T. S., et al. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02455.x · Cited by 276 · see citing works
Nox2-Derived Reactive Oxygen Species Mediate Neurovascular Dysregulation in the Aging Mouse Brain
Park, L., Anrather, J., Girouard, H., Zhou, P., & Iadecola, C. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600491 · Cited by 275 · see citing works
Complete Rescue of Cerebrovascular Function in Aged Alzheimer's Disease Transgenic Mice by Antioxidants and Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist
Nicolakakis, N., Aboulkassim, T., Ongali, B., Lecrux, C., Fernandes, P., Rosa-Neto, P., Tong, X.-K., & Hamel, E. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3348-08.2008 · Cited by 262 · see citing works
Clinicopathologic Studies of Primary Cerebral Amyloid Angiopathy
Okazaki, H., Reagan, T. J., & Campbell, R. J. (1979) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(25)18993-3 · Cited by 259 · see citing works
Reduction in mitochondrial superoxide dismutase modulates Alzheimer’s disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice
Esposito, L., Raber, J., Kekonius, L., Yan, F., Yu, G.-Q., Bien-Ly, N., Puoliväli, J., Scearce-Levie, K., Masliah, E., & Mucke, L. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0482-06.2006 · Cited by 254 · see citing works
NADPH Oxidase-Derived Reactive Oxygen Species Mediate the Cerebrovascular Dysfunction Induced by the Amyloid β Peptide
Park, L., Anrather, J., Zhou, P., Frys, K., Pitstick, R., Younkin, S., Carlson, G. A., & Iadecola, C. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5207-04.2005 · Cited by 244 · see citing works
Aβ1–40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation
Niwa, K., Younkin, L. H., Ebeling, C., Turner, S. K., Westaway, D. A., Younkin, S. G., Ashe, K. H., Carlson, G. A., & Iadecola, C. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.17.9735 · Cited by 244 · see citing works
NADPH oxidases in the vasculature: Molecular features, roles in disease and pharmacological inhibition
Selemidis, S., Sobey, C. G., Wingler, K., Schmidt, H. H. H. W., & Drummond, G. R. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.08.005 · Cited by 241 · see citing works
Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease
Massaad, C. A., Washington, T. M., Pautler, R. G., & Klann, E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902714106 · Cited by 223 · see citing works
Alterations in cerebral blood flow and glucose utilization in mice overexpressing the amyloid precursor protein
Niwa, K., Kazama, K., Younkin, S. G., Carlson, G. A., & Iadecola, C. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0460 · Cited by 218 · see citing works
Aβ-peptides enhance vasoconstriction in cerebral circulation
Niwa, K., Porter, V. A., Kazama, K., Cornfield, D., Carlson, G. A., & Iadecola, C. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.281.6.h2417 · Cited by 202 · see citing works
NADPH oxidase as a therapeutic target in Alzheimer's disease
Block, M. L. (2008) · BMC Neuroscience · doi:10.1186/1471-2202-9-s2-s8 · Cited by 202 · see citing works
Sporadic and Familial Cerebral Amyloid Angiopathies
Révész, T., Holton, J. L., Lashley, T., Plant, G. T., Rostagno, A. A., Ghiso, J. A., & Frangione, B. (2002) · Brain Pathology · doi:10.1111/j.1750-3639.2002.tb00449.x · Cited by 199 · see citing works
Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy
Shin, H. K., Jones, P., Garcı́a-Alloza, M., Borrelli, L. A., Greenberg, S. M., Bacskai, B. J., Frosch, M. P., Hyman, B. T., Moskowitz, M. A., & Ayata, C. (2007) · Brain · doi:10.1093/brain/awm156 · Cited by 192 · see citing works
Exogenous Aβ1–40 Reproduces Cerebrovascular Alterations Resulting from Amyloid Precursor Protein Overexpression in Mice
Niwa, K., Carlson, G. A., & Iadecola, C. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200012000-00005 · Cited by 191 · see citing works
Anti-Aβ antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice
Brendza, R. P., Bacskai, B. J., Cirrito, J. R., Simmons, K. A., Skoch, J. M., Klunk, W. E., Mathis, C. A., Bales, K. R., Paul, S. M., Hyman, B. T., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23269 · Cited by 190 · see citing works
Self-citation
Predominant deposition of amyloid-beta 42(43) in plaques in cases of Alzheimer's disease and hereditary cerebral hemorrhage associated with mutations in the amyloid precursor protein gene.
Mann, D. M. A., Iwatsubo, T., Ihara, Y., Cairns, N. J., Lantos, P. L., Bogdanović, N., Lannfelt, L., Winblad, B. G., Maat–Schieman, M. L. C., & Rossor, M. N. (1996) · Europe PMC (PubMed Central) · Cited by 184 · see citing works
Apolipoprotein E Markedly Facilitates Age-Dependent Cerebral Amyloid Angiopathy and Spontaneous Hemorrhage in Amyloid Precursor Protein Transgenic Mice
Fryer, J. D., Taylor, J. W., DeMattos, R. B., Bales, K. R., Paul, S. M., Parsadanian, M., & Holtzman, D. M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07889.2003 · Cited by 160 · see citing works
Self-citation
Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer?s disease*1Pro-CAA position statement
Nicoll, J. A. R., Yamada, M., Frackowiak, J., Mazur‐Kolecka, B., & Weller, R. O. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.003 · Cited by 159 · see citing works
Modulation of Nuclear Factor-κB Activity by Indomethacin Influences Aβ Levels but Not Aβ Precursor Protein Metabolism in a Model of Alzheimer's Disease
Sung, S., Yang, H., Uryu, K., Lee, E. B., Zhao, L., Shineman, D. W., Trojanowski, J. Q., Lee, V. M. ‐., & Praticò, D. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63269-5 · Cited by 154 · see citing works
Amyloid-β-dependent compromise of microvascular structure and function in a model of Alzheimer’s disease
Dorr, A. E., Sahota, B., Chinta, L. V., Brown, M. E., Lai, A. Y., Ma, K., Hawkes, C. A., McLaurin, J., & Stefanovic, B. (2012) · Brain · doi:10.1093/brain/aws243 · Cited by 153 · see citing works
Vascular Remodeling versus Amyloid β-Induced Oxidative Stress in the Cerebrovascular Dysfunctions Associated with Alzheimer's Disease
Tong, X., Nicolakakis, N., Kocharyan, A., & Hamel, É. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4031-05.2005 · Cited by 153 · see citing works
Rapid Microglial Response Around Amyloid Pathology after Systemic Anti-Aβ Antibody Administration in PDAPP Mice
Koenigsknecht-Talboo, J., Meyer-Luehmann, M., Parsadanian, M., Garcia-Alloza, M., Finn, M. B., Hyman, B. T., Bacskai, B. J., & Holtzman, D. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4147-08.2008 · Cited by 149 · see citing works
Oxidative Metabolites Accelerate Alzheimer's Amyloidogenesis by a Two-Step Mechanism, Eliminating the Requirement for Nucleation
Bieschke, J., Zhang, Q., Powers, E. T., Lerner, R. A., & Kelly, J. W. (2005) · Biochemistry · doi:10.1021/bi0501030 · Cited by 144 · see citing works
Apocynin improves outcome in experimental stroke with a narrow dose range
Tang, X. N., Cairns, B., Cairns, N., & Yenari, M. A. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.03.090 · Cited by 142 · see citing works
Cerebrovascular Dysfunction in Amyloid Precursor Protein Transgenic Mice: Contribution of Soluble and Insoluble Amyloid-β Peptide, Partial Restoration via γ-Secretase Inhibition
Han, B. H., Zhou, M.-L., Abousaleh, F., Brendza, R. P., Dietrich, H. H., Koenigsknecht-Talboo, J., Cirrito, J. R., Milner, E., Holtzman, D. M., & Zipfel, G. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4686-08.2008 · Cited by 138 · see citing works
Self-citation
Structural and Functional Disruption of Vascular Smooth Muscle Cells in a Transgenic Mouse Model of Amyloid Angiopathy
Christie, R. H., Yamada, M., Moskowitz, M. A., & Hyman, B. T. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64053-9 · Cited by 137 · see citing works
Cerebral Amyloid Angiopathy and Vessel Dysfunction
Greenberg, S. M. (2002) · Cerebrovascular Diseases · doi:10.1159/000049149 · Cited by 135 · see citing works
Aβ-Induced Vascular Oxidative Stress and Attenuation of Functional Hyperemia in Mouse Somatosensory Cortex
Park, L., Anrather, J., Forster, C. L., Kazama, K., Carlson, G. A., & Iadecola, C. (2004) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000105800.49957.1e · Cited by 128 · see citing works
Chronic melatonin therapy fails to alter amyloid burden or oxidative damage in old Tg2576 mice: implications for clinical trials
Quinn, J. F., Kulhanek, D. J., Nowlin, J., Jones, R. E., Praticò, D., Rokach, J., & Stackman, R. W. (2005) · Brain Research · doi:10.1016/j.brainres.2005.01.023 · Cited by 114 · see citing works
Nox isoforms in vascular pathophysiology: insights from transgenic and knockout mouse models
Rivera, J., Sobey, C. G., Walduck, A. K., & Drummond, G. R. (2010) · Redox Report · doi:10.1179/174329210x12650506623401 · Cited by 105 · see citing works
Clinical phenotypes of Cerebral Amyloid Angiopathy
Maia, L. F., Mackenzie, I. R., & Feldman, H. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.054 · Cited by 104 · see citing works
Cerebrovascular Effects of Amyloid-ß Peptides: Mechanisms and Implications for Alzheimer's Dementia
Iadecola, C. (2003) · Cellular and Molecular Neurobiology · doi:10.1023/a:1025092617651 · Cited by 92 · see citing works
Mechanisms of Soluble β-Amyloid Impairment of Endothelial Function
Gentile, M. T., Vecchione, C., Maffei, A., Aretini, A., Marino, G., Poulet, R., Capobianco, L., Selvetella, G., & Lembo, G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407358200 · Cited by 91 · see citing works
Apocynin but Not Allopurinol Prevents and Reverses Adrenocorticotropic Hormone-Induced Hypertension in the Rat
Zhang, Y., Chan, M. M. K., Andrews, M. C., Mori, T. A., Croft, K. D., McKenzie, K. U. S., Schyvens, C. G., & WHITWORTH, J. (2005) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2005.02.017 · Cited by 86 · see citing works
Differential vascular functions of Nox family NADPH oxidases
Brandes, R. P., & Schröder, K. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32830c91e3 · Cited by 85 · see citing works
Series Introduction: Alzheimer’s disease: perspectives for the new millennium
Sisodia, S. S. (1999) · Journal of Clinical Investigation · doi:10.1172/jci8508 · Cited by 83 · see citing works
Superoxide free radical and intracellular calcium mediate Aβ1–42 induced endothelial toxicity
Suo, Z., Fang, C., Crawford, F., & Mullan, M. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00383-1 · Cited by 83 · see citing works
Promotion of Amyloid β Protein Misfolding and Fibrillogenesis by a Lipid Oxidation Product
Liu, L., Komatsu, H., Murray, I. V. J., & Axelsen, P. H. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.01.057 · Cited by 81 · see citing works
Physiological levels ofβ-amyloid induce cerebral vessel dysfunction and reduce endothelial nitric oxide production
Price, J. M., Chi, X., Hellermann, G., & Sutton, E. T. (2001) · Neurological Research · doi:10.1179/016164101101198758 · Cited by 80 · see citing works
Soluble amyloid-β, effect on cerebral arteriolar regulation and vascular cells
Dietrich, H. H., Xiang, C., Han, B. H., Zipfel, G. J., & Holtzman, D. M. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-15 · Cited by 77 · see citing works
Self-citation
Matrix metalloproteinase inhibition reduces oxidative stress associated with cerebral amyloid angiopathy in vivo in transgenic mice
García-Alloza, M., Prada, C. M., Lattarulo, C. R., Fine, S., Borrelli, L. A., Betensky, R., Greenberg, S. M., Frosch, M., & Bacskai, B. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06096.x · Cited by 73 · see citing works
Inhibition of Alzheimer's β-Amyloid Induced Vasoactivity and Proinflammatory Response in Microglia by a cGMP-Dependent Mechanism
Paris, D., Town, T., Parker, T. A., Tan, J., Humphrey, J., Crawford, F., & MULLAN, M. J. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7055 · Cited by 71 · see citing works
Nitric oxide in the cerebral cortex of amyloid-precursor protein (SW) Tg2576 transgenic mice
Rodrigo, J., Fernández‐Vizarra, P., Castro‐Blanco, S., Bentura, M. L., Nieto, M., Gómez‐Isla, T., Martínez‐Murillo, R., Martı́nez, A., Serrano, J., & Fernández, A. P. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.06.030 · Cited by 70 · see citing works
Cerebral Amyloid Angiopathy: Progressive Disruption of the Neurovascular Unit
Zipfel, G., Han, H. B., Ford, A., & Lee, J. (2008) · Stroke · doi:10.1161/strokeaha.108.533174 · Cited by 70 · see citing works
Self-citation
Apocynin attenuates tubular apoptosis and tubulointerstitial fibrosis in transgenic mice independent of hypertension
Liu, F., Wei, C., Wu, S.-J., Chénier, I., Zhang, S., Filep, J. G., Ingelfinger, J. R., & Chan, J. S. D. (2008) · Kidney International · doi:10.1038/ki.2008.509 · Cited by 64 · see citing works
Soluble β-amyloid peptides mediate vasoactivity via activation of a pro-inflammatory pathway
Paris, D., Town, T., Mori, T., Parker, T. A., Humphrey, J., & MULLAN, M. J. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00111-6 · Cited by 64 · see citing works
β-Amyloid induces cerebrovascular endothelial dysfunction in the rat brain
Price, J. M., Sutton, T., Hellermann, A., & Thomas, T. (1997) · Neurological Research · doi:10.1080/01616412.1997.11740853 · Cited by 62 · see citing works
Resorufin analogs preferentially bind cerebrovascular amyloid: potential use as imaging ligands for cerebral amyloid angiopathy
Han, B. W., Zhou, M., Vellimana, A. K., Milner, E., Kim, D. H., Greenberg, J. K., Chu, W., Mach, R. H., & Zipfel, G. J. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-86 · Cited by 60 · see citing works
Self-citation
Cerebrovascular endothelial dysfunction mediated by β-amyloid
Thomas, T., McLendon, C., Sutton, E. T., & Thomas, G. (1997) · Neuroreport · doi:10.1097/00001756-199704140-00014 · Cited by 59 · see citing works
Diapocynin and apocynin administration fails to significantly extend survival in G93A SOD1 ALS mice
Trumbull, K. A., McAllister, D. M., Gandelman, M., Fung, W. Y., Lew, T. K., Brennan, L. D., Lopez, N. I., Morré, J. T., Kalyanaraman, B., & Beckman, J. S. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.07.015 · Cited by 56 · see citing works
Cerebral amyloid angiopathy in the elderly: the clinicopathological features, pathogenesis, and risk factors.
Itoh, Y., & Yamada, M. (1997) · PubMed · Cited by 29 · see citing works
Multiphoton microscopy and amyloid angiopathy.
Christie, R. H., Kimchi, E. Y., Kajdasz, S. T., et al. (2001) · PubMed · Cited by 9 · see citing works
Diagnostic criteria for primary progressive mutiple sclerosis: a position paper.
(2000) · Pure Amsterdam UMC · doi:10.1002/1531-8249(200006)47:6 · Cited by 2 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

Holtzman DM, et al. (2000) Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model. Ann Neurol 47(6):739-747.

Sorted by citations

ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease
Simpson, D. S. A., & Oliver, P. L. (2020) · Antioxidants · doi:10.3390/antiox9080743 · Cited by 1,044 · see citing works
“Additionally, human CAA post-mortem capillaries with amyloid-β load are surrounded by NOX2-positive microglia [122,123].”
BackgroundInfluential
NADPH oxidase in brain injury and neurodegenerative disorders
Ma, M. W., Wang, J., Zhang, Q., Wang, R., Dhandapani, K. M., Vadlamudi, R. K., & Brann, D. W. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0150-7 · Cited by 432 · see citing works
Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders
Salvadores, N., Sanhueza, M., Manque, P., & Court, F. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00451 · Cited by 182 · see citing works
APOE immunotherapy reduces cerebral amyloid angiopathy and amyloid plaques while improving cerebrovascular function
Xiong, M., Jiang, H., Serrano, J. R., Gonzales, E. R., Wang, C., Gratuze, M., Hoyle, R., Bien-Ly, N., Silverman, A. P., Sullivan, P. M., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd7522 · Cited by 179 · see citing works
Self-citation
Cerebrovascular resistance: effects on cognitive decline, cortical atrophy, and progression to dementia
Yew, B., Nation, D. A., & Initiative, F. T. A. D. N. (2017) · Brain · doi:10.1093/brain/awx112 · Cited by 133 · see citing works
Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy
Saito, S., Yamamoto, Y., Maki, T., Hattori, Y., Ito, H., Mizuno, K., Harada-Shiba, M., Kalaria, R. N., Fukushima, M., Takahashi, R., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0429-5 · Cited by 110 · see citing works
Nitric Oxide Pathways in Neurovascular Coupling Under Normal and Stress Conditions in the Brain: Strategies to Rescue Aberrant Coupling and Improve Cerebral Blood Flow
Lourenço, C. F., & Laranjinha, J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.729201 · Cited by 85 · see citing works
Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress
Uekawa, K., Hattori, Y., Ahn, S. J., Seo, J., Casey, N., Anfray, A., Zhou, P., Luo, W., Anrather, J., Park, L., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00660-1 · Cited by 80 · see citing works
Toward understanding genomic instability, mitochondrial dysfunction and aging
Fakouri, N. B., Hou, Y., Demarest, T. G., Christiansen, L. S., Okur, M. N., Mohanty, J. G., Croteau, D. L., & Bohr, V. A. (2019) · The FEBS Journal · doi:10.1111/febs.14663 · Cited by 77 · see citing works
p47phox deficiency improves cognitive impairment and attenuates tau hyperphosphorylation in mouse models of AD
Gong, P., Chen, Y.-Q., Lin, A.-H., Zhang, H.-B., Zhang, Y., Ye, R. D., & Yu, Y. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00714-2 · Cited by 29 · see citing works

Cerebral amyloid angiopathy with extensive mineralization.
Mackenzie, I. R. (1997) · PubMed · Cited by 4 · see citing works
On Some Involutional Changes in the Hippocampal Region of the Elderaly Brains
Morimatsu, M. (1975) · Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics · doi:10.3143/geriatrics.12.30
The Impact of Various Reactive Oxygen Species on the Formation of Neutrophil Extracellular Traps
Kirchner, T., Möller, S., Klinger, M. H. F., Solbach, W., Laskay, T., & Behnen, M. (2012) · Mediators of Inflammation · doi:10.1155/2012/849136 · Cited by 231 · see citing works
The association between hypertensive angiopathy and cerebral amyloid angiopathy in primary intracerebral hemorrhage
Zhu, Y., Liu, L., Yu, X., et al. (2023) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2023.122461
Vascular Variant of Alzheimer's Disease Characterized by Severe Plaque-Like β Protein Angiopathy
Yamada, M., Itoh, Y., Suematsu, N., Otomo, E., & Matsushita, M. (1997) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000106626 · Cited by 23 · see citing works

Authors: Han, B. H., Zhou, M.-L., Johnson, A. W., Singh, I., Liao, F., Vellimana, A. K., Nelson, J. W., Milner, E., Cirrito, J. R., Basak, J., Yoo, M., Dietrich, H. H., Holtzman, D. M., & Zipfel, G. J.
Affiliations: Washington University in St. Louis (US)
Departments of aNeurological Surgery,
Neurology, and
ORCID: Zhou, Meng-liang
Johnson, Andrew W.
Singh, Itender
Liao, Fan
Vellimana, Ananth K.
Milner, Eric
Cirrito, John R.
Basak, Jacob
Holtzman, David M.
Zipfel, Gregory Joseph
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2015-02-09
Volume: 112
Issue: 8
Pages: E881-90
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1414930112
PMC: PMC4345564
OpenAlex: W2123684403
Cited by: 131
References: 72
Citations by year: 2026: 4 · 2025: 4 · 2024: 6 · 2023: 10 · 2022: 10 · 2021: 17 · 2020: 17 · 2019: 12 · 2018: 9 · 2017: 16 · 2016: 18 · 2015: 8
FWCI: 11.99
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.pnas.org/site/misc/userlicense.xhtml (vor)
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: HHS | NIH | National Institute of Neurological Disorders and Stroke (NS071011-01A1)
HHS | National Institutes of Health (AG13956)
Topics: Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: cerebral amyloid angiopathy, reactive oxygen species, NADPH oxidase, oxidative stress, vasomotor dysfunction, cerebral microhemorrhages, amyloid-beta, apocynin, tempol, apolipoprotein E, Tg2576 mice, aging, Alzheimer's disease, cerebrovascular dysfunction
MeSH terms: Acetophenones, Aging, Animals, Apolipoproteins E, Astrocytes, Brain, Cerebral Arteries, Cerebral Hemorrhage, Cyclic N-Oxides, Cricetinae, Humans, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Smooth, Vascular, Spin Labels, Vasomotor System, Cerebral Amyloid Angiopathy, Reactive Oxygen Species, Microglia, Oxidative Stress, Myocytes, Smooth Muscle

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

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks