Anti-Aβ antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice

Brendza, Robert P.; Bacskai, Brian J.; Cirrito, John R.; Simmons, Kelly A.; Skoch, Jesse M.; Klunk, William E.; Mathis, Chester A.; Bales, Kelly R.; Paul, Steven M.; Hyman, Bradley T.; Holtzman, David M.

doi:10.1172/jci23269

Cited by 190Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Anti-Aβ antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice

Open access

Brendza, Robert P., Bacskai, Brian J., Cirrito, John R., Simmons, Kelly A., Skoch, Jesse M., Klunk, William E., Mathis, Chester A., Bales, Kelly R. +3 more·2005·Journal of Clinical Investigation

DOI 10.1172/jci23269PMC PMC544607

Open this paper in CoChat — free account Open PDF

Abstract

Neuritic plaques are a defining feature of Alzheimer disease (AD) pathology. These structures are composed of extracellular accumulations of amyloid-beta peptide (Abeta) and other plaque-associated proteins, surrounded by large, swollen axons and dendrites (dystrophic neurites) and activated glia. Dystrophic neurites are thought to disrupt neuronal function, but whether this damage is static, dynamic, or reversible is unknown. To address this, we monitored neuritic plaques in the brains of living PDAPP;Thy-1:YFP transgenic mice, a model that develops AD-like pathology and also stably expresses yellow fluorescent protein (YFP) in a subset of neurons in the brain. Using multiphoton microscopy, we observed and monitored amyloid through cranial windows in PDAPP;Thy-1:YFP double-transgenic mice using the in vivo amyloid-imaging fluorophore methoxy-X04, and individual YFP-labeled dystrophic neurites by their inherent fluorescence. In vivo studies using this system suggest that amyloid-associated dystrophic neurites are relatively stable structures in PDAPP;Thy-1:YFP transgenic mice over several days. However, a significant reduction in the number and size of dystrophic neurites was seen 3 days after Abeta deposits were cleared by anti-Abeta antibody treatment. This analysis suggests that ongoing axonal and dendritic damage is secondary to Abeta and is, in part, rapidly reversible.

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 · 10.1172/jci23269

Cites

6 of 6 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?

Treatment with anti-Aβ antibodies in APP transgenic mice can rapidly resolve some of the neuritic swellings near plaques.
“and even rapidly resolve some of the neuritic swellings near plaques (Brendza et al., 2005).”
From Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy (2005) · cites this paper as Brendza et al., 2005

Self-check

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

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

Triple-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 · see citing works
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease
Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., et al. (2000) · Nature Medicine · doi:10.1038/78682 · Cited by 2,012 · see citing works
Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease
DeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J.-C., Paul, S. M., & Holtzman, D. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151261398 · Cited by 1,298 · see citing works
Self-citation
Reversible memory loss in a mouse transgenic model of Alzheimer’s disease
Kotilinek, L. A., Bacskai, B., Westerman, M., Kawarabayashi, T., Younkin, L., Hyman, B. T., Younkin, S., & Ashe, K. H. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-15-06331.2002 · Cited by 420 · see citing works
Self-citation
Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration
Wilcock, D. M., Munireddy, S. K., Rosenthal, A., Ugen, K. E., Gordon, M. N., & Morgan, D. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.09.015 · Cited by 202 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

Knowles, R.B., et al. 1999. Plaque-induced neurite abnormalities: implications for disruption of neu- ral networks in Alzheimer's disease. Proc. Natl. Acad. Sci. U. S. A. 96:5274-5279.

Sorted by citations

Axon degeneration mechanisms: Commonality amid diversity
Coleman, M. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1788 · Cited by 819 · see citing works
Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy
Spires, T. L., Meyer-Luehmann, M., Stern, E. A., McLean, P. J., Skoch, J., Nguyen, P. T., Bacskai, B. J., & Hyman, B. T. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1879-05.2005 · Cited by 550 · see citing works
“We have recently demonstrated that treatment with anti-Aβ antibodies in APP transgenic mice can remove plaques (Bacskai et al., 2002), straighten the trajectory of neurites (Lombardo et al., 2003) and even rapidly resolve some of the neuritic swellings near plaques (Brendza et al., 2005).”
BackgroundSelf-citation
Microglia Mediate the Clearance of Soluble Aβ through Fluid Phase Macropinocytosis
Mandrekar, S., Jiang, Q., Lee, C. Y. D., Koenigsknecht-Talboo, J., Holtzman, D. M., & Landreth, G. E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5572-08.2009 · Cited by 415 · see citing works
Self-citation
Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease
Nixon, R. A. (2017) · The FASEB Journal · doi:10.1096/fj.201700359 · Cited by 400 · see citing works
Amyloid β Induces the Morphological Neurodegenerative Triad of Spine Loss, Dendritic Simplification, and Neuritic Dystrophies through Calcineurin Activation
Wu, H.-Y., Hudry, E., Hashimoto, T., Kuchibhotla, K., Rozkalne, A., Fan, Z., Spires-Jones, T., Xie, H., Arbel-Ornath, M., Grosskreutz, C. L., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4456-09.2010 · Cited by 367 · see citing works
Self-citation
Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans
Uryu, K., Chen, X.-H., Martinez, D., Browne, K. D., Johnson, V. E., Graham, D. I., Lee, V. M.-Y., Trojanowski, J. Q., & Smith, D. H. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.06.018 · Cited by 360 · see citing works
Aβ Species Removal After Aβ 42 Immunization
Nicoll, J. A. R., Barton, E., Boche, D., Neal, J. W., Ferrer, I., Thompson, P., Vlachouli, C., Wilkinson, D., Bayer, A., Games, D., et al. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000240466.10758.ce · Cited by 265 · 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
Active and passive immunotherapy for neurodegenerative disorders
Brody, D. L., & Holtzman, D. M. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.060407.125529 · Cited by 250 · see citing works
Self-citation
Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer’s disease
Pooler, A. M., Polydoro, M., Maury, E. A., Nicholls, S. B., Reddy, S. M., Wegmann, S., William, C., Saqran, L., Cagsal-Getkin, O., Pitstick, R., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0199-x · Cited by 236 · see citing works
Self-citation
The p75 Neurotrophin Receptor Promotes Amyloid-β(1-42)-Induced Neuritic DystrophyIn VitroandIn Vivo
Knowles, J. K., Rajadas, J., Nguyen, T.-V. V., Yang, T., LeMieux, M. C., Vander Griend, L., Ishikawa, C., Massa, S. M., Wyss-Coray, T., & Longo, F. M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.0620-09.2009 · Cited by 184 · see citing works
Severely dystrophic axons at amyloid plaques remain continuous and connected to viable cell bodies
Adalbert, R., Nogradi, A., Babetto, E., Janeckova, L., Walker, S. A., Kerschensteiner, M., Misgeld, T., & Coleman, M. P. (2009) · Brain · doi:10.1093/brain/awn312 · Cited by 177 · see citing works
Beneficial effect of human anti-amyloid-β active immunization on neurite morphology and tau pathology
Serrano-Pozo, A., William, C. M., Ferrer, I., Uro-Coste, E., Delisle, M.-B., Maurage, C.-A., Hock, C., Nitsch, R. M., Masliah, E., Growdon, J. H., et al. (2010) · Brain · doi:10.1093/brain/awq056 · Cited by 159 · see citing works
Self-citation
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
Tau Passive Immunotherapy in Mutant P301L Mice: Antibody Affinity versus Specificity
d’Abramo, C., Acker, C. M., Jimenez, H. T., & Davies, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062402 · Cited by 144 · 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
Neuropathology after active Aβ42 immunotherapy: implications for Alzheimer’s disease pathogenesis
Boche, D., Denham, N., Holmes, C., & Nicoll, J. A. R. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0719-5 · Cited by 135 · see citing works
Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice
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., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414930112 · Cited by 131 · see citing works
Self-citation
Mitochondrial Dysfunction and Dendritic Beading during Neuronal Toxicity
Greenwood, S. M., Mizielinska, S. M., Frenguelli, B. G., Harvey, J., & Connolly, C. N. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704488200 · Cited by 128 · see citing works
Simvastatin improves cerebrovascular function and counters soluble amyloid-beta, inflammation and oxidative stress in aged APP mice
Tong, X.-K., Nicolakakis, N., Fernandes, P., Ongali, B., Brouillette, J., Quirion, R., & Hamel, E. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.06.003 · Cited by 122 · see citing works
The dendritic hypothesis for Alzheimer's disease pathophysiology
Cochran, J. N., Hall, A. M., & Roberson, E. D. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.12.004 · Cited by 114 · see citing works
Bapineuzumab and solanezumab for Alzheimer's disease: is the ‘amyloid cascade hypothesis’ still alive?
Tayeb, H. O., Murray, E. D., Price, B. H., & Tarazi, F. I. (2013) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2013.789856 · Cited by 119 · see citing works
Insights into the mechanisms of action of anti‐Aβ antibodies in Alzheimer's disease mouse models
Levites, Y., Smithson, L. A., Price, R. W., Dakin, R. S., Yuan, B., Sierks, M. R., Kim, J., McGowan, E., Kim Reed, D., Rosenberry, T. L., et al. (2006) · The FASEB Journal · doi:10.1096/fj.06-6463fje · Cited by 113 · see citing works
Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer’s Disease
García-Morales, V., González-Acedo, A., Melguizo-Rodríguez, L., Pardo-Moreno, T., Costela-Ruiz, V. J., Montiel-Troya, M., & Ramos-Rodríguez, J. J. (2021) · Biomedicines · doi:10.3390/biomedicines9121910 · Cited by 104 · see citing works
Plaque-derived oxidative stress mediates distorted neurite trajectories in the Alzheimer mouse model
Garcia-Alloza, M., Dodwell, S. A., Meyer-Luehmann, M., Hyman, B. T., & Bacskai, B. J. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000240468.12543.af · Cited by 99 · see citing works
Self-citation
Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer’s and other neurodegenerative diseases
Golde, T. E., & Miller, V. M. (2009) · Alzheimer's Research & Therapy · doi:10.1186/alzrt5 · Cited by 98 · see citing works
Reduction of aggregated Tau in neuronal processes but not in the cell bodies after Aβ42 immunisation in Alzheimer’s disease
Boche, D., Donald, J., Love, S., Harris, S., Neal, J. W., Holmes, C., & Nicoll, J. A. R. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0705-y · Cited by 85 · see citing works
Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice
Perez, S. E., He, B., Muhammad, N., Oh, K.-J., Fahnestock, M., Ikonomovic, M. D., & Mufson, E. J. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.10.002 · Cited by 80 · see citing works
Aerosol Delivery of Curcumin Reduced Amyloid-β Deposition and Improved Cognitive Performance in a Transgenic Model of Alzheimer’s Disease
McClure, R., Ong, H., Janve, V., Barton, S., Zhu, M., Li, B., Dawes, M., Jerome, W. G., Anderson, A., Massion, P., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160289 · Cited by 54 · see citing works
Impact of increased APP gene dose in Down syndrome and the Dp16 mouse model
Sawa, M., Overk, C., Becker, A., Derse, D., Albay, R., Weldy, K., Salehi, A., Beach, T. G., Doran, E., Head, E., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12463 · Cited by 54 · see citing works
Selective vulnerability of different types of commissural neurons for amyloid -protein-induced neurodegeneration in APP23 mice correlates with dendritic tree morphology
Capetillo-Zarate, E., Staufenbiel, M., Abramowski, D., Haass, C., Escher, A., Stadelmann, C., Yamaguchi, H., Wiestler, O. D., & Thal, D. R. (2006) · Brain · doi:10.1093/brain/awl176 · Cited by 45 · see citing works
In vivo characterization of a bigenic fluorescent mouse model of Alzheimer’s disease with neurodegeneration
Crowe, S. E., & Ellis‐Davies, G. C. R. (2013) · Journal of Comparative Neurology · doi:10.1002/cne.23306 · Cited by 15 · see citing works

Authors: 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., & Holtzman, D. M.
Affiliations: Washington University in St. Louis (US)
Harvard University (US)
University of Pittsburgh (US)
Eli Lilly (United States) (US)
Corresponding author: Holtzman, David M.
ORCID: Bacskai, Brian J.
Cirrito, John R.
Skoch, Jesse M.
Klunk, William E.
Mathis, Chester A.
Paul, Steven M.
Hyman, Bradley T.
Holtzman, David M.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2005-01-20
Volume: 115
Issue: 2
Pages: 428-433
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci23269
PMC: PMC544607
OpenAlex: W2126885422
Cited by: 190
References: 6
Citations by year: 2026: 3 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 2 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 2 · 2013: 10 · 2012: 7
FWCI: 15.69
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
Funders: Alzheimer's Association (EB00768, AG13956)
American Health Assistance Foundation
Eli Lilly and Company
National Institutes of Health (AG13956, AG08487)
National Institute on Aging (AG20222, AG-08487, R01AG020222, R01AG013956, R01AG008487, R01AG020570, R37AG013956, AG13956, AG 020570)
National Institute of Neurological Disorders and Stroke (P01NS032636)
National Institute of Biomedical Imaging and Bioengineering (EB-00768, R01EB000768)
Topics: Health Sciences › Medicine › Physiology › 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: amyloid-beta, neuritic plaques, dystrophic neurites, Alzheimer's disease
MeSH terms: Alzheimer Disease, Animals, Antibodies, Monoclonal, Mice, Transgenic, Radiography, Neurites, Amyloid beta-Protein Precursor, Neuroaxonal Dystrophies, Tomography, Optical, Mice, 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

Anti-Aβ antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Record

About these checks