Involvement of perineuronal and perisynaptic extracellular matrix in Alzheimer's disease neuropathology

Morawski, Markus; Brückner, Gert; Jäger, Carsten; Seeger, Gudrun; Matthews, Russel T; Arendt, Thomas

doi:10.1111/j.1750-3639.2011.00557.x

Cited by 157Alzheimer's disease research and treatmentsProteoglycans and glycosaminoglycans researchNeuroscience and Neuropharmacology Research

Involvement of perineuronal and perisynaptic extracellular matrix in Alzheimer's disease neuropathology

Open access

Morawski, Markus, Brückner, Gert, Jäger, Carsten, Seeger, Gudrun, Matthews, Russel T, Arendt, Thomas·2012·Brain Pathology

DOI 10.1111/j.1750-3639.2011.00557.xPMC PMC3639011

Open this paper in CoChat — free account

Abstract

Brain extracellular matrix (ECM) is organized in specific patterns assumed to mirror local features of neuronal activity and synaptic plasticity. Aggrecan‐based perineuronal nets (PNs) and brevican‐based perisynaptic axonal coats (ACs) form major structural phenotypes of ECM contributing to the laminar characteristics of cortical areas. In Alzheimer's disease (AD), the deposition of amyloid proteins and processes related to neurofibrillary degeneration may affect the integrity of the ECM scaffold. In this study we investigate ECM organization in primary sensory, secondary and associative areas of the temporal and occipital lobe. By detecting all major PN components we show that the distribution, structure and molecular properties of PNs remain unchanged in AD. Intact PNs occurred in close proximity to amyloid plaques and were even located within their territory. Counting of PNs revealed no significant alteration in AD. Moreover, neurofibrillary tangles never occurred in neurons associated with PNs. ACs were only lost in the core of amyloid plaques in parallel with the loss of synaptic profiles. In contrast, hyaluronan was enriched in the majority of plaques. We conclude that the loss of brevican is associated with the loss of synapses, whereas PNs and related matrix components resist disintegration and may protect neurons from degeneration.

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 · 10.1111/j.1750-3639.2011.00557.x

Cites

105 of 105 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?

Most previous studies support a beneficial role of PNN in Alzheimer's disease mouse models.
“In summary, most of the previous studies are in support of beneficial role of PNN in AD mouse model.”
From Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis (2020) · cites this paper as Morawski et al., 2012
The Discussion (Functional implications; page not provided) describes potential neuroprotective actions of perineuronal nets, including protection against amyloid toxicity in vitro. The Discussion (Area-specific laminar distribution patterns; page not provided) also cites one AD mouse-model study in which perineuronal nets were largely unchanged. These passages do not establish that most previous studies found a beneficial role in AD mouse models. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Loss of PNN CS-GAGs appears to occur independently to PNN core proteins (aggrecan and brevican), which remain stable in postmortem AD brain tissue.
“Intriguingly, the loss of PNN CS-GAGs appears to occur independently to PNN core proteins (i.e., aggrecan and brevican), which remain stable in postmortem AD brain tissue (Brückner et al. 1999; Morawski et al. 2010a; Morawski et al. 2012; Lendvai et al. 2013; Howell et al. 2015).”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Morawski et al. 2012
The Discussion (Technical considerations; page not available) reports that prolonged post-mortem delay substantially reduced WFA binding to chondroitin-associated sites while aggrecan reactivity was virtually unaffected. But it attributes that loss to post-mortem changes, not AD: WFA and VVA binding was retained in well-preserved AD and control tissue. The paper also identifies brevican with perisynaptic axonal coats rather than PNNs and reports its loss in plaque cores. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Neurons with intact PNN never deposit neurofibrillary tangles.
“neurons having intact PNN never deposits neurofibrillary tangles (Morawski et al., 2012)”
From Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis (2020) · cites this paper as Morawski et al., 2012
Whether perineuronal nets are altered in Alzheimer's disease remains controversial.
“but whether PNNs are altered in AD remains controversial.”
From Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain (2020) · cites this paper as [42]
In Alzheimer's disease, cortical and subcortical neurons enwrapped by a perineuronal net are less frequently affected by neurofibrillary degeneration than neurons without a perineuronal net.
“In previous studies we could demonstrate that in AD cortical and subcortical neurons are constantly less frequently affected by neurofibrillary degeneration if they are enwrapped by a specialized form of the ECM, the so-called PN.2, 3”
From Aggrecan, link protein and tenascin-R are essential components of the perineuronal net to protect neurons against iron-induced oxidative stress (2014) · cites this paper as [3]

Self-check

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

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

Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 3× · see citing works
“Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes.”
MethodInfluential
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer's disease
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397 · see citing works
Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator
West, M. J., Slomianka, L., & Gundersen, H. J. G. (1991) · The Anatomical Record · doi:10.1002/ar.1092310411 · Cited by 2,994 · see citing works
Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex
Pizzorusso, T., Medini, P., Berardi, N., Chierzi, S., Fawcett, J. W., & Maffei, L. (2002) · Science · doi:10.1126/science.1072699 · Cited by 1,679 · see citing works
Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles
Wiedenmann, B. J., & Franke, W. W. (1985) · Cell · doi:10.1016/s0092-8674(85)80082-9 · Cited by 1,432 · see citing works
Atlas of the Human Brain
Jeurgen, K., Assheuer, J., & Paxinos, G. (1997) · Medical Entomology and Zoology · Cited by 1,403 · see citing works
The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease
Arnold, S. E., Hyman, B. T., Flory, J., Damasio, A. R., & Van Hoesen, G. W. (1991) · Cerebral Cortex · doi:10.1093/cercor/1.1.103 · Cited by 1,380 · see citing works
Amyloid-β and tau — a toxic pas de deux in Alzheimer's disease
Ittner, L. M., & Götz, J. (2010) · Nature reviews. Neuroscience · doi:10.1038/nrn2967 · Cited by 1,357 · see citing works
The Rhesus Monkey Brain in Stereotaxic Coordinates
Paxinos, G., Huang, X., & Toga, A. W. (1999) · Research Online (University of Wollongong) · Cited by 1,070 · see citing works
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 · see citing works
Neuropathology of Alzheimer's Disease
Perl, D. P. (2010) · Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine · doi:10.1002/msj.20157 · Cited by 825 · see citing works
Molecular mechanisms of neurodegeneration in Alzheimer's disease
Crews, L., & Masliah, E. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq160 · Cited by 772 · cited 1× · see citing works
“Extracellular deposition of amyloid and intracellular neurofibrillary changes, formed by tau-aggregation, are hallmarks of Alzheimer’s disease (AD) (24, 49).”
Background
Tau protein and the neurofibrillary pathology of Alzheimer's disease
Goedert, M. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90078-z · Cited by 718 · see citing works
Matrix metalloproteinases and their multiple roles in neurodegenerative diseases
Rosenberg, G. A. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70016-x · Cited by 594 · see citing works
Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer’s disease: a quantitative study of visual and auditory cortices
Lewis, D., Campbell, M., Terry, R., & Morrison, J. (1987) · The Journal of Neuroscience · doi:10.1523/jneurosci.07-06-01799.1987 · Cited by 578 · see citing works
Extracellular matrix molecules and synaptic plasticity
Dityatev, A., & Schachner, M. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1115 · Cited by 564 · see citing works
The dual role of the extracellular matrix in synaptic plasticity and homeostasis
Dityatev, A., Schachner, M., & Sonderegger, P. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2898 · Cited by 559 · see citing works
Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity
Frischknecht, R., Heine, M., Perrais, D., Seidenbecher, C. I., Choquet, D., & Gundelfinger, E. D. (2009) · Nature Neuroscience · doi:10.1038/nn.2338 · Cited by 554 · see citing works
The stress of dieting
Hutchinson, E. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn2985 · Cited by 534 · see citing works
Animals lacking link protein have attenuated perineuronal nets and persistent plasticity
Carulli, D., Pizzorusso, T., Kwok, J. C. F., Putignano, E., Poli, A., Forostyak, S., Andrews, M. R., Deepa, S. S., Glant, T. T., & Fawcett, J. W. (2010) · Brain · doi:10.1093/brain/awq145 · Cited by 495 · see citing works
Calcium-binding protein parvalbumin as a neuronal marker
Celio, M. R., & Heizmann, C. W. (1981) · Nature · doi:10.1038/293300a0 · Cited by 486 · see citing works
The glial glutamate transporter, GLT‐1, is oxidatively modified by 4‐hydroxy‐2‐nonenal in the Alzheimer's disease brain: the role of Aβ1–42
Lauderback, C. M., Hackett, J. M., Huang, F. F., Keller, J. N., Szweda, L. I., Markesbery, W. R., & Butterfield, D. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00451.x · Cited by 464 · see citing works
Wisteria floribunda agglutinin-labelled nets surround parvalbumin-containing neurons
Härtig, W., Brauer, K., & Brückner, G. (1992) · NeuroReport · doi:10.1097/00001756-199210000-00012 · Cited by 440 · see citing works
Self-citation
Matrix Metalloproteinases Expressed by Astrocytes Mediate Extracellular Amyloid-β Peptide Catabolism
Yin, K.-J., Cirrito, J. R., Yan, P., Hu, X., Xiao, Q., Pan, X., Bateman, R., Song, H., Hsu, F.-F., Turk, J., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2085-06.2006 · Cited by 381 · see citing works
Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer's disease: identification of phosphorylation sites in tau protein
Goedert, M., Jakes, R., Crowther, R. A., Cohen, P., Vanmechelen, E., Vandermeeren, M., & Cras, P. (1994) · Biochemical Journal · doi:10.1042/bj3010871 · Cited by 375 · see citing works
Perineuronal nets provide a polyanionic, glia‐associated form of microenvironment around certain neurons in many parts of the rat brain
Brückner, G., Brauer, K., Härtig, W., Wolff, J. R., Rickmann, M. J., Derouiche, A., Delpech, B., Girard, N., Oertel, W. H., & Reichenbach, A. (1993) · Glia · doi:10.1002/glia.440080306 · Cited by 358 · see citing works
Self-citation
Glutaminyl cyclase inhibition attenuates pyroglutamate Aβ and Alzheimer's disease–like pathology
Schilling, S., Zeitschel, U., Hoffmann, T., Heiser, U., Francke, M., Kehlen, A., Holzer, M., Hutter-Paier, B., Prokesch, M., Windisch, M., et al. (2008) · Nature Medicine · doi:10.1038/nm.1872 · Cited by 357 · see citing works
Cortical neurons immunoreactive for the potassium channel Kv3.1b subunit are predominantly surrounded by perineuronal nets presumed as a buffering system for cations
Härtig, W., Derouiche, A., Welt, K., Brauer, K., Grosche, J., Mäder, M., Reichenbach, A., & Brückner, G. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01784-9 · Cited by 339 · see citing works
Self-citation
Mutations in the neuronal β-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects
Poirier, K., Saillour, Y., Bahi‐Buisson, N., Jaglin, X. H., Fallet‐Bianco, C., Nabbout, R., Castelnau, L., Roubertie, A., Attié‐Bitach, T., Desguerre, I., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq377 · Cited by 273 · see citing works
Sensory Deprivation Alters Aggrecan and Perineuronal Net Expression in the Mouse Barrel Cortex
McRae, P. A., Rocco, M. M., Kelly, G., Brumberg, J. C., & Matthews, R. T. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5425-06.2007 · Cited by 272 · see citing works
Self-citation
Expression of neural proteoglycans correlates with the acquisition of mature neuronal properties in the mammalian brain
Hockfield, S., Kalb, R. G., Zaremba, S., & Fryer, H. (1990) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1990.055.01.049 · Cited by 271 · see citing works
Molecular signals of plasticity at the tetrapartite synapse
Dityatev, A., & Rusakov, D. A. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.12.006 · Cited by 267 · see citing works
The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007
Beach, T., Sue, L., Walker, D., Roher, A., Lue, L., Vedders, L. J., Connor, D., Sabbagh, M., & Rogers, J. (2007) · Cell and Tissue Banking · doi:10.1007/s10561-008-9067-2 · Cited by 265 · see citing works
Synapse loss in the temporal lobe in Alzheimer's disease
Scheff, S. W., & PRICE, D. A. (1993) · Annals of Neurology · doi:10.1002/ana.410330209 · Cited by 263 · see citing works
Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index
Henson, D. E., Ries, L. A. G., Freedman, L. S., & Carriaga, M. T. (1991) · Cancer · doi:10.1002/1097-0142(19911115)68:10 · Cited by 253 · see citing works
Perineuronal nets potentially protect against oxidative stress
Morawski, M., Brückner, M. K., Riederer, P., Brückner, G., & Arendt, T. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.04.017 · Cited by 246 · see citing works
Self-citation
Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer’s disease
Urbanc, B., Cruz, L., Le, R., Sanders, J., Ashe, K. H., Duff, K., Stanley, H. E., Irizarry, M. C., & Hyman, B. T. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222433299 · Cited by 237 · see citing works
Compartmentalization from the outside: the extracellular matrix and functional microdomains in the brain
Dityatev, A. E., Seidenbecher, C. I., & Schachner, M. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.08.003 · Cited by 229 · see citing works
The Extracellular Matrix Molecule Hyaluronic Acid Regulates Hippocampal Synaptic Plasticity by Modulating Postsynaptic L-Type Ca2+ Channels
Kochlamazashvili, G., Henneberger, C., Bukalo, O., Dvoretskova, E., Senkov, O., Lievens, P. M.-J., Westenbroek, R., Engel, A. K., Catterall, W. A., Rusakov, D. A., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.05.030 · Cited by 215 · see citing works
Perineuronal net formation and structure in aggrecan knockout mice
Giamanco, K. A., Morawski, M., & Matthews, R. T. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.08.032 · Cited by 207 · see citing works
Self-citation
Oxidative damage to extracellular matrix and its role in human pathologies
Rees, M. D., Kennett, E. C., Whitelock, J. M., & Davies, M. J. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.03.016 · Cited by 206 · see citing works
Matrix metalloproteases and their inhibitors are produced by overlapping populations of activated astrocytes
Muir, E. M., Adcock, K. H., Morgenstern, D. A., Clayton, R., von Stillfried, N., Rhodes, K., Ellis, C., Fawcett, J. W., & Rogers, J. H. (2002) · Molecular Brain Research · doi:10.1016/s0169-328x(02)00132-8 · Cited by 206 · see citing works
Extracellular matrix components associated with remodeling processes in brain
Rauch, U. (2004) · Cellular and Molecular Life Sciences (CMLS) · doi:10.1007/s00018-004-4043-x · Cited by 205 · see citing works
Brain-enriched Hyaluronan Binding (BEHAB)/Brevican Cleavage in a Glioma Cell Line Is Mediated by a Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) Family Member
Matthews, R. T., Gary, S. C., Zerillo, C. A., Pratta, M. A., Solomon, K. A., Arner, E. C., & Hockfield, S. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m909764199 · Cited by 197 · see citing works
Self-citation
Cortical areas abundant in extracellular matrix chondroitin sulphate proteoglycans are less affected by cytoskeletal changes in Alzheimer's disease
Brückner, G., Hausen, D., Härtig, W., Drlicek, M., Arendt, T., & Brauer, K. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00071-8 · Cited by 196 · see citing works
Self-citation
Parvalbumin-lmmunoreactive Neurons in the Neocortex are Resistant to Degeneration in Alzheimerʼs Disease
HOF, P. R., COX, K., Young, W. G., Celio, M. R., Rogers, J., & Morrison, J. H. (1991) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199107000-00006 · Cited by 188 · see citing works
Chondroitin Sulfate Proteoglycans Are Associated with the Lesions of Alzheimer's Disease
DeWitt, D. A., Silver, J., Canning, D. R., & Perry, G. L. (1993) · Experimental Neurology · doi:10.1006/exnr.1993.1081 · Cited by 182 · see citing works
Degradation of Amyloid β-Protein by a Metalloprotease Secreted by Microglia and Other Neural and Non-neural Cells
Qiu, W. Q., Ye, Z., Kholodenko, D., Seubert, P. A., & Selkoe, D. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.10.6641 · Cited by 175 · see citing works
Macrophage/Microglia-specific Protein Iba1 Enhances Membrane Ruffling and Rac Activation via Phospholipase C-γ-dependent Pathway
Kanazawa, H., Ohsawa, K., Sasaki, Y., Kohsaka, S., & Imai, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109218200 · Cited by 170 · see citing works
Acute and long-lasting changes in extracellular-matrix chondroitin-sulphate proteoglycans induced by injection of chondroitinase ABC in the adult rat brain
Brückner, G., Bringmann, A., Härtig, W., Köppe, G., Delpech, B., & Brauer, K. (1998) · Experimental Brain Research · doi:10.1007/s002210050463 · Cited by 162 · see citing works
Self-citation
Interaction of Tau Isoforms with Alzheimer's Disease Abnormally Hyperphosphorylated Tau and in VitroPhosphorylation into the Disease-like Protein
Alonso, A. D. C., Zaidi, T., Novák, M., Barra, H. S., Grundke, I., & Iqbal, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105365200 · Cited by 160 · see citing works
Upregulation of aggrecan, link protein 1, and hyaluronan synthases during formation of perineuronal nets in the rat cerebellum
Carulli, D., Rhodes, K. E., & Fawcett, J. W. (2007) · Journal of Comparative Neurology · doi:10.1002/cne.21231 · Cited by 158 · see citing works
Neurons associated with aggrecan-based perineuronal nets are protected against tau pathology in subcortical regions in Alzheimer's disease
Morawski, M., Brückner, G., Jäger, C., Seeger, G., & Arendt, T. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.05.022 · Cited by 156 · see citing works
Self-citation
Amyloidogenesis: historical and modern observations point to heparan sulfate proteoglycans as a major culprit
Ancsin, J. B. (2003) · Amyloid · doi:10.3109/13506120309041728 · Cited by 156 · see citing works
Inhibitory Role for Dual Specificity Phosphatase VHR in T Cell Antigen Receptor and CD28-induced Erk and Jnk Activation
Alonso, A., Saxena, M., Williams, S., & Mustelin, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006497200 · Cited by 149 · see citing works
Chondroitin sulfate proteoglycan-immunoreactivity of lectin-labeled perineuronal nets around parvalbumin-containing neurons
Ha¨rtig, W., Brauer, K., Bigl, V., & Bru¨ckner, G. (1994) · Brain Research · doi:10.1016/0006-8993(94)91452-4 · Cited by 147 · see citing works
Spatial relationship between synapse loss and β‐amyloid deposition in Tg2576 mice
Dong, H., Martin, M. V., Chambers, S., & Csernansky, J. G. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.21176 · Cited by 146 · see citing works
The link proteins
Neame, P. J., & Barry, F. (1993) · Cellular and Molecular Life Sciences · doi:10.1007/bf01923584 · Cited by 146 · see citing works
Alzheimer's disease: areal and laminar pathology in the occipital isocortex
Braak, H., Braak, E., & Kalus, P. (1989) · Acta Neuropathologica · doi:10.1007/bf00687251 · Cited by 141 · see citing works
Role of hyaluronan in glioma invasion
Park, J. B., Kwak, H., & Lee, S. (2008) · Cell Adhesion & Migration · doi:10.4161/cam.2.3.6320 · Cited by 136 · see citing works
Amyloid accomplices and enforcers
Alexandrescu, A. T. (2004) · Protein Science · doi:10.1110/ps.04887005 · Cited by 134 · see citing works
Vesicle-associated membrane protein-2 (synaptobrevin-2) forms a complex with synaptophysin
Washbourne, P., Schiavo, G., & Montecucco, C. (1995) · Biochemical Journal · doi:10.1042/bj3050721 · Cited by 133 · see citing works
Role of proteoglycans and glycosaminoglycans in the pathogenesis of Alzheimer's disease and related disorders: Amyloidogenesis and therapeutic strategies—A review
Ariga, T., Miyatake, T., & Yu, R. K. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22393 · Cited by 128 · see citing works
Lamina-specific arrangement of astrocytic gliosis and senile plaques in Alzheimer's disease visual cortex
Beach, T. G., & McGeer, E. G. (1988) · Brain Research · doi:10.1016/0006-8993(88)90410-6 · Cited by 123 · see citing works
Changes in extracellular space size and geometry in APP23 transgenic mice: A model of Alzheimer's disease
Syková, E., Voříšek, I., Antonova, T., Mazel, T., Meyer-Luehmann, M., Jucker, M., Hájek, M., Or, M., & Bureš, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408235102 · Cited by 121 · see citing works
Loss of parvalbumin-immunoreactive neurones from cortex in Alzheimer-type dementia
Arai, H., Emson, P. C., Mountjoy, C. Q., Carassco, L. H., & Heizmann, C. W. (1987) · Brain Research · doi:10.1016/0006-8993(87)90974-7 · Cited by 118 · see citing works
Epitope mapping of mAbs AT8 and Tau5 directed against hyperphosphorylated regions of the human tau protein
Porzig, R., Singer, D. L., & Hoffmann, R. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.04.187 · Cited by 117 · see citing works
Region and lamina-specific distribution of extracellular matrix proteoglycans, hyaluronan and tenascin-R in the mouse hippocampal formation
Brückner, G., Grosche, J., Hartlage‐Rübsamen, M., Schmidt, S., & Schachner, M. (2003) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(03)00036-x · Cited by 116 · see citing works
Self-citation
Tau Protein and the Neurofibrillary Pathology of Alzheimer's Disease
Goedert, M. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34410.x · Cited by 115 · see citing works
Human glioblastomas overexpress ADAMTS-5 that degrades brevican
Nakada, M., Miyamori, H., Kita, D., Takahashi, T., Yamashita, J., Sato, H., Miura, R., Yamaguchi, Y., & Okada, Y. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-1032-6 · Cited by 113 · see citing works
Loss of perineuronal net N-acetylgalactosamine in Alzheimer’s disease
Baig, S., Wilcock, G. K., & Love, S. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-1060-2 · Cited by 112 · see citing works
Morphological diversities of CD44 positive astrocytes in the cerebral cortex of normal subjects and patients with Alzheimer's disease
Akiyama, H., Tooyama, I., Kawamata, T., Ikeda, K., & McGeer, P. L. (1993) · Brain Research · doi:10.1016/0006-8993(93)91160-t · Cited by 107 · see citing works
Decomposition and long-lasting downregulation of extracellular matrix in perineuronal nets induced by focal cerebral ischemia in rats.
Hobohm, C., Günther, A., Grosche, J., Roßner, S., Schneider, D., & Brückner, G. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20459 · Cited by 103 · see citing works
Self-citation
Quantitative Distribution of Parvalbumin, Calretinin, and Calbindin D-28k Immunoreactive Neurons in the Visual Cortex of Normal and Alzheimer Cases
Leuba, G., Kraftsik, R., & Saini, K. (1998) · Experimental Neurology · doi:10.1006/exnr.1998.6838 · Cited by 101 · see citing works
Perineuronal nets protect against amyloid β-protein neurotoxicity in cultured cortical neurons
Miyata, S., Nishimura, Y., & Nakashima, T. (2007) · Brain Research · doi:10.1016/j.brainres.2007.02.066 · Cited by 101 · see citing works
Characterization of proteoglycan-containing perineuronal nets by enzymatic treatments of rat brain sections
Köppe, G., Brückner, G., Härtig, W., Delpech, B., & Bigl, V. (1997) · The Histochemical Journal · doi:10.1023/a:1026408716522 · Cited by 95 · see citing works
Self-citation
Aggrecan-based extracellular matrix is an integral part of the human basal ganglia circuit
Brückner, G., Morawski, M., & Arendt, T. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.10.033 · Cited by 90 · see citing works
Self-citation
Immunohistochemical localization of hyaluronic acid in rat and human brain
Yasuhara, O., Akiyama, H., McGeer, E. G., & McGeer, P. L. (1994) · Brain Research · doi:10.1016/0006-8993(94)91448-6 · Cited by 74 · see citing works
Parvalbumin immunoreactive neurons in normal human temporal neocortex and in patients with Alzheimer's disease
Ferrer, I., Soriano, E., Tuñón, T., Fonseca, M., & Guionnet, N. (1991) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(91)90250-b · Cited by 72 · see citing works
ADAMTS-4 (aggrecanase-1): N-Terminal activation mechanisms
Tortorella, M. D., Arner, E. C., Hills, R. L., Gormley, J. A., Fok, K. F., Pegg, L. E., Munie, G. E., & Malfait, A. (2005) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2005.09.018 · Cited by 70 · see citing works
Glutaminyl cyclase contributes to the formation of focal and diffuse pyroglutamate (pGlu)-Aβ deposits in hippocampus via distinct cellular mechanisms
Hartlage‐Rübsamen, M., Morawski, M., Waniek, A., Jäger, C., Zeitschel, U., Koch, B. C. P., Cynis, H., Schilling, S., Schliebs, R., Demuth, H., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0806-2 · Cited by 66 · see citing works
Self-citation
Protease inhibitor coinfusion with amyloid β-protein results in enhanced deposition and toxicity in rat brain
Frautschy, S. A., Horn, D. L., Sigel, J. J., Harris-White, M. E., Mendoza, J. J., Yang, F., Saido, T. C., & Cole, G. M. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-20-08311.1998 · Cited by 65 · see citing works
Chondroitin sulfate proteoglycans protect cultured rat's cortical and hippocampal neurons from delayed cell death induced by excitatory amino acids
Okamoto, M., Mori, S., Ichimura, M., & Endô, H. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90660-2 · Cited by 52 · see citing works
Amyloidosis: new strategies for treatment.
Hirschfield, G., & Hawkins, P. (2003) · International Journal of Biochemistry and Cell Biology · doi:10.1016/s1357-2725(03)00169-9 · Cited by 51 · see citing works
Molecular differences among neurons reveal an organization of human visual cortex.
Hockfield, S. J., Tootell, R. B. H., & Zaremba, S. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.8.3027 · Cited by 51 · see citing works
ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs) is transcriptionally induced in beta-amyloid treated rat astrocytes
Satoh, K., Suzuki, N., & Yokota, H. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01285-4 · Cited by 51 · see citing works
Dystrophic neurites in TgCRND8 and Tg2576 mice mimic human pathological brain aging
Woodhouse, A., Vickers, J. C., Adlard, P. A., & Dickson, T. C. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.09.003 · Cited by 50 · see citing works
Perineuronal nets are largely unaffected in Alzheimer model Tg2576 mice
Morawski, M., Pavlica, S., Seeger, G., Grosche, J., Kouznetsova, E., Schliebs, R., Brückner, G., & Arendt, T. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.07.023 · Cited by 49 · see citing works
Self-citation
Perineuronal nets in the rhesus monkey and human basal forebrain including basal ganglia
Adams, I., Brauer, K., Arélin, C., Härtig, W., Fine, A., Mäder, M., Arendt, T., & Brückner, G. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00419-5 · Cited by 48 · see citing works
Self-citation
Vicia villosa lectin-positive neurones in human cerebral cortex. Loss in Alzheimer-type dementia
Kobayashi, K., Emson, P. C., & Mountjoy, C. Q. (1989) · Brain Research · doi:10.1016/0006-8993(89)90416-2 · Cited by 48 · see citing works
Hyperphosphorylated protein tau is restricted to neurons devoid of perineuronal nets in the cortex of aged bison⋆
Härtig, W. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00179-2 · Cited by 46 · see citing works
Distribution patterns of Wisteria floribunda agglutinin binding sites and parvalbumin-immunoreactive neurons in the human visual cortex: a double-labelling study.
Seeger, G., Lüth, H. J., Winkelmann, E., & Brauer, K. (1996) · PubMed · Cited by 46 · see citing works
Self-citation
Abnormal post‐translational and extracellular processing of brevican in plaque‐bearing mice over‐expressing APPsw
Ajmo, J. M., Bailey, L. A., Howell, M. D., Cortez, L. K., Pennypacker, K. R., Mehta, H. N., Morgan, D., Gordon, M. N., & Gottschall, P. E. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06647.x · Cited by 41 · see citing works
Distinct glutaminyl cyclase expression in Edinger–Westphal nucleus, locus coeruleus and nucleus basalis Meynert contributes to pGlu-Aβ pathology in Alzheimer’s disease
Morawski, M., Hartlage‐Rübsamen, M., Jäger, C., Waniek, A., Schilling, S., Schwab, C., McGeer, P. L., Arendt, T., Demuth, H., & Roßner, S. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0685-y · Cited by 37 · see citing works
Self-citation
Differential distribution of aggrecan isoforms in perineuronal nets of the human cerebral cortex
Virgintino, D., Perissinotto, D., Girolamo, F., Mucignat, M. T., Montanini, L., Errede, M., Kaneiwa, T., Yamada, S., Sugahara, K., Roncali, L., et al. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00694.x · Cited by 36 · see citing works
Glycosaminoglycans in Cortical Autopsy Samples from Alzheimer Brain
Jenkins, H. G., & Bachelard, H. S. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb01135.x · Cited by 36 · see citing works
Chondroitin sulfate reduces cell death of rat hippocampal slices subjected to oxygen and glucose deprivation by inhibiting p38, NFκB and iNOS
Martin‐de‐Saavedra, M. D., del Barrio, L., Cañas, N., Egea, J., Lorrio, S., Montell, E., Vergés, J., Garcı́a, A. G., & López, M. G. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.02.006 · Cited by 28 · see citing works
Aggrecan-based extracellular matrix shows unique cortical features and conserved subcortical principles of mammalian brain organization in the Madagascan lesser hedgehog tenrec (Echinops telfairi Martin, 1838)
Morawski, M., Brückner, G., Jäger, C., Seeger, G., Künzle, H., & Arendt, T. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.08.018 · Cited by 28 · see citing works
Self-citation
The link proteins
Neame, P. J., & Barry, F. (1994) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-7545-5_5 · Cited by 23 · see citing works
The Extracellular Matrix in the Mouse Brain. Its Reactions to Endo-Alpha-N-Acetylgalactosaminidase and Certain Other Enzymes.
MURAKAMI, T., Ohtsuka, A., Su, W., TAGUCHI, T., Oohashi, T., Murakami, T., Abe, K., & Ninomiya, Y. (1999) · Archivum histologicum japonicum · doi:10.1679/aohc.62.273 · Cited by 21 · see citing works
A role for extracellular matrix degradation and matrix metalloproteinases in senile dementia?
Bignami, A., LeBlanc, A. C., & Perides, G. (1994) · Acta Neuropathologica · doi:10.1007/bf00296747 · Cited by 20 · see citing works
β-Amyloid Fibrillation and/or Hyperhomocysteinemia Modify Striatal Patterns of Hyaluronic Acid and Dermatan Sulfate: Possible Role in the Pathogenesis of Alzheimers Disease
Genedani, S., Agnati, L. F., Leo, G., et al. (2010) · Current Alzheimer Research · doi:10.2174/156720510790691074 · Cited by 20 · see citing works
The Binding of Iron to Perineuronal Nets: A Combined Nuclear Microscopy and Mössbauer Study
Morawski, M., Reinert, T., Brückner, G., Wagner, F. E., Arendt, T. H., & Tröger, W. (2005) · Hyperfine Interactions · doi:10.1007/s10751-005-9116-1 · Cited by 12 · see citing works
Self-citation
Loss of perineuronal net N-acetylgalactosamine in Alzheimer’s disease
Baig, S., Wilcock, G. K., & Love, S. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0080-x · Cited by 8 · see citing works

Flagged first, then by citations

Sorted by citations

Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
Zhang, B., Gaiteri, C., Bodea, L.-G., Wang, Z., McElwee, J., Podtelezhnikov, A. A., Zhang, C., Xie, T., Tran, L., Dobrin, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.030 · Cited by 1,657 · see citing works
The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function
Fawcett, J. W., Oohashi, T., & Pizzorusso, T. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0196-3 · Cited by 589 · see citing works
Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain
Crapser, J. D., Spangenberg, E. E., Barahona, R. A., Arreola, M. A., Hohsfield, L. A., & Green, K. N. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102919 · Cited by 280 · see citing works
Proteomic differences in amyloid plaques in rapidly progressive and sporadic Alzheimer’s disease
Drummond, E., Nayak, S., Faustin, A., Pires, G., Hickman, R. A., Askenazi, M., Cohen, M., Haldiman, T., Kim, C., Han, X., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1691-0 · Cited by 239 · see citing works
Analyzing dendritic spine pathology in Alzheimer’s disease: Problems and opportunities
Dorostkar, M. M., Zou, C., Blazquez-Llorca, L., & Herms, J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1449-5 · Cited by 235 · see citing works
Aggrecan, link protein and tenascin-R are essential components of the perineuronal net to protect neurons against iron-induced oxidative stress
Suttkus, A., Rohn, S., Weigel, S., Glöckner, P., Arendt, T., & Morawski, M. (2014) · Cell Death & Disease · doi:10.1038/cddis.2014.25 · Cited by 168 · see citing works
Self-citation
Chondroitin sulfates and their binding molecules in the central nervous system
Djerbal, L., Lortat-Jacob, H., & Kwok, J. (2017) · Glycoconjugate Journal · doi:10.1007/s10719-017-9761-z · Cited by 144 · see citing works
Neuron-Glia Interactions in Neural Plasticity: Contributions of Neural Extracellular Matrix and Perineuronal Nets
Dzyubenko, E., Gottschling, C., & Faissner, A. (2016) · Neural Plasticity · doi:10.1155/2016/5214961 · Cited by 134 · see citing works
Aggrecan: Beyond cartilage and into the brain
Morawski, M., Brückner, G., Arendt, T., & Matthews, R. T. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.01.010 · Cited by 136 · see citing works
Self-citation
Perineuronal nets and schizophrenia: The importance of neuronal coatings
Bitanihirwe, B. K. Y., & Woo, T.-U. W. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.03.018 · Cited by 95 · see citing works
Neurochemical mapping of the human hippocampus reveals perisynaptic matrix around functional synapses in Alzheimer’s disease.
Lendvai, D., Morawski, M., Négyessy, L., Gáti, G., Jäger, C., Baksa, G., Glasz, T., Attems, J., Tanila, H., Arendt, T., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-012-1042-0 · Cited by 93 · see citing works
Self-citation
ECM in brain aging and dementia
Morawski, M., Filippov, M., Tzinia, A., Tsilibary, E., & Vargova, L. (2014) · Progress in Brain Research · doi:10.1016/b978-0-444-63486-3.00010-4 · Cited by 84 · see citing works
Self-citation
Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration
Yang, S., Hilton, S., Alves, J. N., Saksida, L. M., Bussey, T., Matthews, R. T., Kitagawa, H., Spillantini, M. G., Kwok, J. C. F., & Fawcett, J. W. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.08.002 · Cited by 61 · see citing works
Self-citation
Molecular heterogeneity of aggrecan-based perineuronal nets around five subclasses of parvalbumin-expressing neurons in the mouse hippocampus.
Yamada, J., & Jinno, S. (2017) · Journal of Comparative Neurology · doi:10.1002/cne.24132 · Cited by 59 · see citing works
Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep
Härtig, W., Mages, B., Aleithe, S., Nitzsche, B., Altmann, S., Barthel, H., Krueger, M., & Michalski, D. (2017) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2017.00015 · Cited by 53 · see citing works
Decreased Density of Perineuronal Net in Prelimbic Cortex Is Linked to Depressive-Like Behavior in Young-Aged Rats
Yu, Z., Chen, N., Hu, D., Chen, W., Yuan, Y., Meng, S., Zhang, W., Lu, L., Han, Y., & Shi, J. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00004 · Cited by 52 · see citing works
Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration
Logsdon, A. F., Foresi, B., Hu, S. J., Quah, E., Meuret, C. J., Le, J. P., Hendrickson, A. S., Redford, I. K., Kumar, A., Phan, B. A., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16067 · Cited by 16 · see citing works
Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis
Al-Amin, M. M., Grandjean, J., Klohs, J., & Kim, J. (2020) · doi:10.1101/2020.04.27.064634 · Cited by 2 · see citing works
“For instance, neurons having intact PNN never deposits neurofibrillary tangles (Morawski et al., 2012); PNN prevents Aβ-induced neurotoxicity in cortical neurons (Miyata et al., 2007) and neurons with aggrecan-linked PNN protect tau pathology (Morawski et al., 2010a).”
Background

Perineuronal net formation and structure in aggrecan knockout mice
Giamanco, K. A., Morawski, M., & Matthews, R. T. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.08.032 · Cited by 207 · see citing works
Self-citation
<i>In vitro</i> modeling of perineuronal nets: hyaluronan synthase and link protein are necessary for their formation and integrity
Kwok, J. C. F., Carulli, D., & Fawcett, J. W. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06878.x · Cited by 170 · see citing works
Hyaluronan degradation and release of a hyaluronan-aggrecan complex from perineuronal nets in the aged mouse brain
Sugitani, K., Egorova, D., Mizumoto, S., Nishio, S., Yamada, S., Kitagawa, H., Oshima, K., Nadano, D., Matsuda, T., & Miyata, S. (2021) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2020.129804 · Cited by 28 · see citing works
Aggrecan Glycoforms Contribute to the Molecular Heterogeneity of Perineuronal Nets
Matthews, R. T., Kelly, G. M., Zerillo, C. A., Gray, G., Tiemeyer, M., & Hockfield, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-17-07536.2002 · Cited by 341 · see citing works
Self-citation
Expression of aggrecan components in perineuronal nets in the mouse cerebral cortex
Ueno, H., Fujii, K., Suemitsu, S., Murakami, S., Kitamura, N., Wani, K., Aoki, S., Okamoto, M., Ishihara, T., & Takao, K. (2018) · IBRO Reports · doi:10.1016/j.ibror.2018.01.002 · Cited by 47 · see citing works

Authors: Morawski, M., Brückner, G., Jäger, C., Seeger, G., Matthews, R. T., & Arendt, T.
Affiliations: Leipzig University (DE)
SUNY Upstate Medical University (US)
ORCID: Morawski, Markus
Arendt, Thomas
Venue: Brain Pathology
Publisher: Wiley
Published: 2012-01-13
Volume: 22
Issue: 4
Pages: 547-561
ISSN: 1015-6305 (ISSN-L)
1750-3639
DOI: 10.1111/j.1750-3639.2011.00557.x
PMC: PMC3639011
OpenAlex: W1543143540
Cited by: 157
References: 105
Citations by year: 2026: 6 · 2025: 10 · 2024: 17 · 2023: 9 · 2022: 11 · 2021: 14 · 2020: 16 · 2019: 6 · 2018: 14 · 2017: 10 · 2016: 9 · 2015: 8 · 2014: 12 · 2013: 10 · 2012: 5
FWCI: 5.80
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Brain Pathology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
Funders: National Institute on Aging (P30AG019610)
National Institute of Neurological Disorders and Stroke (U24NS072026)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: Alzheimer's disease, extracellular matrix, perineuronal nets, brevican, aggrecan, hyaluronic acid, amyloid plaques, neurofibrillary tangles, synaptic loss, temporal lobe, occipital lobe, cortical laminar organization
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Axons, Brain, Extracellular Matrix, Female, Humans, Male, Synapses, Microscopy, Confocal, Aggrecans, Brevican

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

Involvement of perineuronal and perisynaptic extracellular matrix in Alzheimer's disease neuropathology

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks