Computational modeling of tau pathology spread reveals patterns of regional vulnerability and the impact of a genetic risk factor
Open accessPublished version of a preprint
Abstract
Spread of tau pathology follows brain connectivity, is modulated by selective vulnerability, and is predicted by network analysis.
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
Cites
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?
Advances in image registration and analysis of serial sections improve capacity for complete unbiased assessment.
“Advances in image registration and analysis of serial sections improve this capacity (Furth et al., 2018; Cornblath et al., 2021), but remain laborious and limited to a subset of anatomical levels.”
From Spontaneous pathology in PS19 tauopathy mice progresses via brain networks (2025) · cites this paper as Cornblath et al., 2021
The Results section, “Quantitative immunohistochemistry to evaluate pathological tau spread” (page unavailable), describes quantifying two sets of nearby sections to reduce selection bias. The Materials and Methods section, “Quantitative pathology” (page unavailable), describes digital analysis but also says annotations were modified by hand on sections selected at six anatomical levels. These passages support improved regional assessment through section analysis, but not an advance in image registration or a complete, unbiased assessment. (LLM, conf=0.84)
Experimental — accuracy not yet measuredBy registering whole brain images of p-tau deposition in PS19 mice into the annotated Allen CCFv3, we identified seven regions which consistently exhibited pathology at 6mo and all later ages.
“By registering whole brain images of p-tau deposition in PS19 mice into the annotated Allen CCFv3, similar to recent studies (Whitesell et al., 2019; Cornblath et al., 2021), we identified seven regions which consistently exhibited pathology at 6mo and all later ages.”
From Spontaneous pathology in PS19 tauopathy mice progresses via brain networks (2025) · cites this paper as Cornblath et al., 2021
The Results section says Cornblath et al. quantified phosphorylated tau pathology in brain regions annotated using the Allen CCF v3. The Methods section describes manually matching annotations to selected coronal sections, not registering whole-brain images into the atlas. The seven regions in PS19 mice are the citing authors’ own finding, not a finding attributed to Cornblath et al. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172 · see citing works
Dorsey, E. R., Elbaz, A., Nichols, E., Abbasi, N., Abd-Allah, F., Abdelalim, A., Adsuar, J. C., Ansha, M. G., Brayne, C., Choi, J.-Y. J., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30295-3 · Cited by 2,816 · see citing works
A mesoscale connectome of the mouse brain
Oh, S. W., Harris, J. A., Ng, L., Winslow, B., Cain, N., Mihalas, S., Wang, Q., Lau, C., Kuan, L., Henry, A. M., et al. (2014) · Nature · doi:10.1038/nature13186 · Cited by 2,612 · see citing works
Nalls, M. A., Blauwendraat, C., Vallerga, C. L., Heilbron, K., Bandres-Ciga, S., Chang, D., Tan, M., Kia, D. A., Noyce, A. J., Xue, A., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30320-5 · Cited by 2,454 · see citing works
Nichols, E., Szoeke, C. E. I., Vollset, S. E., Abbasi, N., Abd-Allah, F., Abdela, J., Aichour, M. T. E., Akinyemi, R. O., Alahdab, F., Asgedom, S. W., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30403-4 · Cited by 2,412 · see citing works
Healy, D. G., Falchi, M., O’Sullivan, S. S., Bonifati, V., Dürr, A., Bressman, S., Brice, A., Aasly, J. O., Zabetian, C. P., Goldwurm, S., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70117-0 · Cited by 1,523 · see citing works
Saman, S., Kim, W., Raya, M., Visnick, Y., Miro, S., Saman, S., Jackson, B., McKee, A. C., Alvarez, V. E., Lee, N. C. Y., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.277061 · Cited by 985 · see citing works
Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds
Holmes, B. B., DeVos, S. L., Kfoury, N., Li, M., Jacks, R., Yanamandra, K., Ouidja, M. O., Brodsky, F. M., Marasa, J., Bagchi, D. P., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301440110 · Cited by 859 · see citing works
Neuronal activity enhances tau propagation and tau pathology in vivo
Wu, J. W., Hussaini, S. A., Bastille, I. M., Rodriguez, G. A., Mrejeru, A., Rilett, K., Sanders, D. W., Cook, C., Fu, H., Boonen, R. A. C. M., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4328 · Cited by 820 · see citing works
The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans
Holth, J. K., Fritschi, S. K., Wang, C., Pedersen, N. P., Cirrito, J. R., Mahan, T. E., Finn, M. B., Manis, M., Geerling, J. C., Fuller, P. M., et al. (2019) · Science · doi:10.1126/science.aav2546 · Cited by 813 · see citing works
Robinson, J. L., Lee, E. B., Xie, S. X., Rennert, L., Suh, E., Bredenberg, C., Caswell, C., Van Deerlin, V. M., Yan, N., Yousef, A., et al. (2018) · Brain · doi:10.1093/brain/awy146 · Cited by 729 · see citing works
Self-citationA network diffusion model of disease progression in dementia
Raj, A., Kuceyeski, A., & Weiner, M. (2012) · Neuron · doi:10.1016/j.neuron.2011.12.040 · Cited by 723 · see citing works
The release and trans-synaptic transmission of Tau via exosomes
Wang, Y., Balaji, V., Kaniyappan, S., Krüger, L., Irsen, S., Tepper, K., Chandupatla, R., Maetzler, W., Schneider, A., Mandelkow, E., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0143-y · Cited by 674 · see citing works
Irwin, D. J., Grossman, M., Weintraub, D. A., Hurtig, H. I., Duda, J. E., Xie, S. X., Lee, E. B., Deerlin, V. M. V., López, O. L., Kofler, J., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30291-5 · Cited by 588 · see citing works
Self-citationLRRK2 activation in idiopathic Parkinson’s disease
Maio, R. D., Hoffman, E. K., Rocha, E. M., Keeney, M. T., Sanders, L. H., Miranda, B. R. D., Zharikov, A., Laar, A. D. V., Stepan, A. F., Lanz, T. A., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aar5429 · Cited by 571 · see citing works
LRP1 is a master regulator of tau uptake and spread
Rauch, J. N., Luna, G., Guzman, E., Audouard, M., Challis, C., Sibih, Y. E., Leshuk, C., Hernandez, I., Wegmann, S., Hyman, B. T., et al. (2020) · Nature · doi:10.1038/s41586-020-2156-5 · Cited by 541 · see citing works
Mutant LRRK2R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's disease
Li, Y., Liu, W., Oo, T. F., Wang, L., Tang, Y. L., Jackson-Lewis, V. R., Zhou, C., Geghman, K. D., Bogdanov, M. B., Przedborski, S., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2349 · Cited by 533 · see citing works
Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease
Vogel, J. W., Iturria‐Medina, Y., Strandberg, O. T., Smith, R. A., Levitis, E., Evans, A. C., Hansson, O., Initiative, A. D. N., Weiner, M. W., Aisen, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15701-2 · Cited by 521 · see citing works
Self-citationNeuropathologic substrates of Parkinson disease dementia
Irwin, D. J., White, M. T., Toledo, J. B., Xie, S. X., Robinson, J. L., Van Deerlin, V., Lee, V. M. ‐., Leverenz, J. B., Montine, T. J., Duda, J. E., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23659 · Cited by 518 · see citing works
Self-citationGuo, J. L., Narasimhan, S., Changolkar, L., He, Z., Stieber, A., Zhang, B., Gathagan, R. J., Iba, M., McBride, J. D., Trojanowski, J. Q., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20160833 · Cited by 440 · see citing works
Self-citationClinical Correlations With Lewy Body Pathology inLRRK2-Related Parkinson Disease
Kalia, L. V., Lang, A. E., Hazrati, L., Fujioka, S., Wszołek, Z. K., Dickson, D. W., Ross, O. A., Deerlin, V. M. V., Trojanowski, J. Q., Hurtig, H. I., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.2704 · Cited by 385 · see citing works
Self-citationDzamko, N. L., Deák, M., Hentati, F., Reith, A. D., Prescott, A. R., Alessi, D. R., & Nichols, R. J. (2010) · Biochemical Journal · doi:10.1042/bj20100784 · Cited by 379 · see citing works
Narasimhan, S., Guo, J. L., Changolkar, L., Stieber, A., McBride, J. D., Silva, L. V., He, Z., Zhang, B., Gathagan, R. J., Trojanowski, J. Q., et al. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.1230-17.2017 · Cited by 374 · see citing works
Self-citationSheng, Z., Zhang, S., Bustos, D. J., Kleinheinz, T., Pichon, C. E. L., Domínguez, S. L., Solanoy, H. O., Drummond, J., Zhang, X., Ding, X., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004485 · Cited by 348 · see citing works
Li, X., Patel, J. C., Wang, J., Avshalumov, M. V., Nicholson, C., Buxbaum, J. D., Elder, G. A., Rice, M. E., & Yue, Z. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5604-09.2010 · Cited by 342 · see citing works
Henderson, M. X., Cornblath, E. J., Darwich, A., Zhang, B., Brown, H., Gathagan, R. J., Sandler, R. M., Bassett, D. S., Trojanowski, J. Q., & Lee, V. M. Y. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0457-5 · Cited by 310 · see citing works
Self-citationFell, M. J., Mirescu, C., Basu, K., Cheewatrakoolpong, B., DeMong, D. E., Ellis, J. M., Hyde, L. A., Lin, Y., Markgraf, C. G., Mei, H., et al. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.227587 · Cited by 310 · see citing works
The neuropathology of genetic Parkinson's disease
Poulopoulos, M., Levy, O. A., & Alcalay, R. N. (2012) · Movement Disorders · doi:10.1002/mds.24962 · Cited by 306 · see citing works
Melrose, H. L., Dächsel, J. C., Behrouz, B., Lincoln, S. J., Yue, M., Hinkle, K. M., Kent, C., Korvatska, O., Taylor, J. P., Witten, L. M., et al. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.07.010 · Cited by 273 · see citing works
Unconventional Secretion Mediates the Trans-cellular Spreading of Tau
Katsinelos, T., Zeitler, M., Dimou, E., Karakatsani, A., Müller, H., Nachman, E., Steringer, J. P., de Almodóvar, C. R., Nickel, W., & Jahn, T. R. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.056 · Cited by 252 · see citing works
Usenovic, M., Niroomand, S., Drolet, R. E., Yao, L., Gaspar, R. C., Hatcher, N. G., Schachter, J., Renger, J. J., & Parmentier-Batteur, S. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1523-15.2015 · Cited by 245 · see citing works
Multimodal gradients across mouse cortex
Fulcher, B., Murray, J. D., Zerbi, V., & Wang, X. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814144116 · Cited by 217 · see citing works
Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs)
Rauch, J. N., Chen, J. J., Sorum, A. W., Miller, G. M., Sharf, T., See, S. K., Hsieh-Wilson, L. C., Kampmann, M., & Kosik, K. S. (2018) · Scientific Reports · doi:10.1038/s41598-018-24904-z · Cited by 211 · see citing works
Characterization of Two VQIXXK Motifs for Tau Fibrillization in Vitro
Li, W., & Lee, V. M. ‐. (2006) · Biochemistry · doi:10.1021/bi061422+ · Cited by 197 · see citing works
Self-citationLin, C., Tsai, P.-I., Wu, R., & Chien, C. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1737-10.2010 · Cited by 169 · see citing works
Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non‐Ashkenazi Jewish ancestry
Lee, A., Wang, Y., Alcalay, R. N., Mejia‐Santana, H., Saunders-Pullman, R. J., Bressman, S., Corvol, J., Brice, A., Lesage, S., Mangone, G., et al. (2017) · Movement Disorders · doi:10.1002/mds.27059 · Cited by 164 · see citing works
Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease
Henderson, M. X., Sengupta, M., Trojanowski, J. Q., & Lee, V. M. ‐. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0836-x · Cited by 160 · see citing works
Self-citationCognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders
Coughlin, D. G., Xie, S. X., Liang, M., Williams, A., Peterson, C. S., Weintraub, D. A., McMillan, C. T., Wolk, D. A., Akhtar, R. S., Hurtig, H. I., et al. (2018) · Annals of Neurology · doi:10.1002/ana.25392 · Cited by 145 · see citing works
Self-citationPrion-like spreading of Alzheimer’s disease within the brain’s connectome
Fornari, S., Schäfer, A., Jucker, M., Goriely, A., & Ellen Kuhl, A. (2019) · Journal of The Royal Society Interface · doi:10.1098/rsif.2019.0356 · Cited by 137 · see citing works
Schapansky, J., Khasnavis, S., DeAndrade, M. P., Nardozzi, J. D., Falkson, S. R., Boyd, J. D., Sanderson, J. B., Bartels, T., Melrose, H. L., & LaVoie, M. J. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.12.005 · Cited by 133 · see citing works
Matikainen‐Ankney, B. A., Kezunovic, N., Mesias, R., Tian, Y., Williams, F. M. K., Huntley, G. W., & Benson, D. L. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3314-15.2016 · Cited by 131 · see citing works
Pathological Influences on Clinical Heterogeneity in Lewy Body Diseases
Coughlin, D. G., Hurtig, H. I., & Irwin, D. J. (2019) · Movement Disorders · doi:10.1002/mds.27867 · Cited by 130 · see citing works
Beccano-Kelly, D. A., Kuhlmann, N., Tatarnikov, I., Volta, M., Munsie, L. N., Chou, P., Cao, L.-P., Han, H., Tapia, L., Farrer, M. J., et al. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00301 · Cited by 125 · see citing works
Weickenmeier, J., Jucker, M., Goriely, A., & Ellen Kuhl, A. (2018) · Journal of the Mechanics and Physics of Solids · doi:10.1016/j.jmps.2018.10.013 · Cited by 124 · see citing works
Kawakami, F., Takatoshi, Y., Ohta, E., Maekawa, T., Shimada, N., Suzuki, M., Maruyama, H., Ichikawa, T., & Obata, F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030834 · Cited by 122 · see citing works
Concordance for Parkinson's disease in twins: A 20‐year update
Goldman, S. M., MAREK, K. L., Ottman, R., Meng, C., Comyns, K., Chan, P., Ma, J., Marras, C., Langston, J. W., Ross, G. W., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25441 · Cited by 114 · see citing works
Patient-Tailored, Connectivity-Based Forecasts of Spreading Brain Atrophy
Brown, J. A., Deng, J., Neuhaus, J. M., Sible, I. J., Sias, A. C., Lee, S. E., Kornak, J., Marx, G. A., Karydas, A. M., Spina, S., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.08.037 · Cited by 112 · see citing works
Mezias, C., Rey, N. L., Brundin, P., & Raj, A. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104623 · Cited by 106 · see citing works
LRRK2 phosphorylates novel tau epitopes and promotes tauopathy
Bailey, R. M., Covy, J. P., Melrose, H. L., Rousseau, L., Watkinson, R., Knight, J. A., Miles, S., Farrer, M. J., Dickson, D. W., Giasson, B. I., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1188-4 · Cited by 103 · see citing works
Ossenkoppele, R., Iaccarino, L., Schonhaut, D. R., Brown, J. A., Joie, R. L., O’Neil, J. P., Janabi, M., Baker, S. L., Kramer, J. H., Gorno‐Tempini, M., et al. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101848 · Cited by 103 · see citing works
An Introduction to Second-Generation p -Values
Blume, J. D., Greevy, R. A., Welty, V. F., Smith, J. R., & Dupont, W. D. (2019) · The American Statistician · doi:10.1080/00031305.2018.1537893 · Cited by 91 · see citing works
Ohta, E., Nihira, T., Uchino, A., Imaizumi, Y., Okada, Y., Akamatsu, W., Takahashi, K., Hayakawa, H., Nagai, M., Ohyama, M., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv212 · Cited by 70 · see citing works
McAllister, B. B., Lacoursiere, S. G., Sutherland, R. J., & Mohajerani, M. H. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.01.026 · Cited by 47 · see citing works
LRRK2 activity does not dramatically alter α-synuclein pathology in primary neurons
Henderson, M. X., Peng, C., Trojanowski, J. Q., & Lee, V. M. ‐. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0550-0 · Cited by 46 · see citing works
Self-citationG2019S LRRK2 enhances the neuronal transmission of tau in the mouse brain
Nguyen, A. P. T., Daniel, G., Valdés, P., Islam, M. S., Schneider, B. L., & Moore, D. J. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx389 · Cited by 44 · see citing works
Genetic analysis of neurodegenerative diseases in a pathology cohort
Blauwendraat, C., Pletniková, O., Geiger, J. T., Murphy, N. A., Abramzon, Y. A., Rudow, G. L., Mamais, A., Sabir, M. S., Crain, B. J., Ahmed, S., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.11.007 · Cited by 43 · see citing works
The effect of phenotypic outliers and non-normality on rare-variant association testing
Auer, P. L., Reiner, A. P., & Leal, S. M. (2016) · European Journal of Human Genetics · doi:10.1038/ejhg.2015.270 · Cited by 37 · see citing works
Predictive Model of Spread of Progressive Supranuclear Palsy Using Directional Network Diffusion
Pandya, S., Mezias, C., & Raj, A. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00692 · Cited by 37 · see citing works
Mezias, C., LoCastro, E., Xia, C. N., & Raj, A. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0459-z · Cited by 33 · see citing works
LRRK2 Facilitates tau Phosphorylation through Strong Interaction with tau and cdk5
Shanley, M. R., Hawley, D., Leung, S., Zaidi, N. F., Dave, R., Schlosser, K. A., Bandopadhyay, R., Gerber, S. A., & Liu, M. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00326 · Cited by 30 · see citing works
Lack of exacerbation of neurodegeneration in a double transgenic mouse model of mutant LRRK2 and tau
Mikhail, F., Calingasan, N. Y., Parolari, L., Subramanian, A., Yang, L., & Beal, M. F. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv105 · Cited by 24 · see citing works
Physiologically relevant factors influence tau phosphorylation by leucine‐rich repeat kinase 2
Hamm, M. J., Bailey, R. M., Shaw, G., Yen, S.-H. C., Lewis, J. M., & Giasson, B. I. (2015) · Journal of Neuroscience Research · doi:10.1002/jnr.23614 · Cited by 22 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [53]W. H. R. Chan, M. Wildemeersch, T. Q. S. Quek, Characterization and control of diffusion processes in multi-agent networks. arXiv: https://arxiv.org/abs/1508.06738 [cs.SI] (27 August 2015). · arXiv
Cited by
Sorted by citations
Vogel, J. W., Corriveau‐Lecavalier, N., Franzmeier, N., Pereira, J. B., Brown, J. A., Maaß, A., Botha, H., Seeley, W. W., Bassett, D. S., Jones, D. T., et al. (2023) · Nature reviews. Neuroscience · doi:10.1038/s41583-023-00731-8 · Cited by 160 · see citing works
Self-citationLocal molecular and global connectomic contributions to cross-disorder cortical abnormalities
Hansen, J. Y., Shafiei, G., Vogel, J. W., Smart, K. A., Bearden, C. E., Hoogman, M., Franke, B., van Rooij, D., Buitelaar, J. K., McDonald, C. R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32420-y · Cited by 125 · see citing works
Imaging transcriptomics of brain disorders
Arnatkeviciute, A., Fulcher, B. D., Bellgrove, M. A., & Fornito, A. (2022) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2021.10.002 · Cited by 113 · see citing works
Frontzkowski, L. K., Ewers, M., Brendel, M., Biel, D., Ossenkoppele, R., Hager, P., Steward, A., Dewenter, A., Roemer, S. N., Rubinski, A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32592-7 · Cited by 91 · see citing works
Propagation of tau and α-synuclein in the brain: therapeutic potential of the glymphatic system
Lopes, D. M., Llewellyn, S. K., & Harrison, I. F. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00293-2 · Cited by 74 · see citing works
Montal, V., Diez, I., Kim, C.-M., Orwig, W., Bueichekú, E., Gutiérrez-Zúñiga, R., Bejanin, A., Pegueroles, J., Dols-Icardo, O., Vannini, P., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abn7273 · Cited by 52 · see citing works
Tau follows principal axes of functional and structural brain organization in Alzheimer’s disease
Ottoy, J., Kang, M. S., Tan, J. X. M., Boone, L., de Wael, R. V., Park, B., Bezgin, G., Lussier, F. Z., Pascoal, T. A., Rahmouni, N., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49300-2 · Cited by 49 · see citing works
Tau Seeding Mouse Models with Patient Brain-Derived Aggregates
Robert, A., Schöll, M., & Vogels, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116132 · Cited by 35 · see citing works
Learning interpretable dynamics of stochastic complex systems from experimental data
Gao, T.-T., Barzel, B., & Yan, G. F. (2024) · Nature Communications · doi:10.1038/s41467-024-50378-x · Cited by 32 · see citing works
Network models to enhance the translational impact of cross-species studies
Brynildsen, J. K., Rajan, K., Henderson, M. X., & Bassett, D. S. (2023) · Nature reviews. Neuroscience · doi:10.1038/s41583-023-00720-x · Cited by 29 · see citing works
Self-citationHarris, G. A., Hirschfeld, L. R., González, M. I., Pritchard, M. C., & May, P. C. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01775-x · Cited by 31 · see citing works
Clinical relevance of animal models in aging-related dementia research
Padmanabhan, P., & Götz, J. (2023) · Nature Aging · doi:10.1038/s43587-023-00402-4 · Cited by 28 · see citing works
Dues, D. J., Nguyen, A. P. T., Becker, K., Ma, J., & Moore, D. J. (2023) · npj Parkinson s Disease · doi:10.1038/s41531-023-00574-1 · Cited by 27 · see citing works
α-Synuclein pathology and mitochondrial dysfunction: Toxic partners in Parkinson's disease
Mingo, Y. B., Galvis, M. L. E., & Henderson, M. X. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106889 · Cited by 27 · see citing works
Self-citationBrain network dynamics codify heterogeneity in seizure evolution
Rungratsameetaweemana, N., Lainscsek, C. S. M., Cash, S. S., Garcia, J. O., B, T. J. S. A., & Bansal, K. (2022) · Brain Communications · doi:10.1093/braincomms/fcac234 · Cited by 25 · see citing works
The emerging role of LRRK2 in tauopathies
Herbst, S., Lewis, P. A., & Morris, H. R. (2022) · Clinical Science · doi:10.1042/cs20220067 · Cited by 23 · see citing works
LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression
Lubben, N., Brynildsen, J. K., Webb, C. M., Li, H. L., Leyns, C. E. G., Changolkar, L. N., Zhang, B., Meymand, E. S., O’Reilly, M., Madaj, Z. B., et al. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00403-2 · Cited by 22 · see citing works
Self-citationDon't forget to be picky – selective autophagy of protein aggregates in neurodegenerative diseases
Simonsen, A., & Wollert, T. (2022) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2022.01.009 · Cited by 21 · see citing works
Tau kinetics in Alzheimer's disease
Hier, D. B., Azizi, S., Thimgan, M. S., & Wunsch, D. C. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1055170 · Cited by 21 · see citing works
Lee, W. J., Cho, H., Baek, M. S., Kim, H., Lee, J., Ryu, Y. H., Lyoo, C. H., & Seong, J. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01061-0 · Cited by 20 · see citing works
Puangmalai, N., Bhatt, N. N., Bittar, A., Jerez, C., Shchankin, N., & Kayed, R. (2023) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2023.102562 · Cited by 17 · see citing works
Kumar, T., Sethuraman, R., Mitra, S., Ravindran, B., & Narayanan, M. (2023) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1011022 · Cited by 18 · see citing works
Personalised regional modelling predicts tau progression in the human brain
Chaggar, P., Vogel, J. W., Binette, A. P., Thompson, T., Strandberg, O. T., Mattsson, N., Karlsson, L., Stomrud, E., Jbabdi, S., Magon, S., et al. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003241 · Cited by 17 · see citing works
The Bidirectional Relationship Between Epilepsy and Alzheimer’s Disease
Stewart, D., & Johnson, E. L. (2025) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-025-01404-y · Cited by 16 · see citing works
Computational model for disease research
Chen, X., & Li, H. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbac615 · Cited by 16 · see citing works
Self-citationTau trajectory in Alzheimer’s disease: Evidence from the connectome-based computational models
Bitra, V. R., Challa, S. R., Adiukwu, P. C., & Rapaka, D. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.110777 · Cited by 14 · see citing works
Seed structure and phosphorylation in the fuzzy coat impact tau seeding competency
Kasen, A., Lövestam, S., Breton, E., Meyerdirk, L. K., McPhail, J. A., Piché, K., Louwrier, A., Capan, C. D., Lee, H., Scheres, S. H. W., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64312-2 · Cited by 13 · see citing works
Self-citationBasheer, N., Buée, L., Brion, J., Smolek, T., Muhammadi, M. K., Hritz, J., Hromádka, T., Dewachter, I., Wegmann, S., Landrieu, I., et al. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01748-5 · Cited by 11 · see citing works
Transdiagnostic prevention in youth mental health, Part I: rationale, shared risk factors
Holt, D. J., Choi, K. W., DeTore, N. R., & Balogun‐Mwangi, O. (2025) · Neuropsychopharmacology · doi:10.1038/s41386-025-02233-w · Cited by 11 · see citing works
Endogenous pathology in tauopathy mice progresses via brain networksPreprint
Ramirez, D. M. O., Whitesell, J. D., Bhagwat, N., Thomas, T. L., Ajay, A. D., Nawaby, A., Delatour, B., Bay, S., Lafaye, P. J., Knox, J. E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.23.541792 · Cited by 9 · see citing works
Limitations and Applications of Rodent Models in Tauopathy and Synucleinopathy Research
Szegvari, E., Holec, S. A. M., & Woerman, A. L. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70021 · Cited by 8 · see citing works
MSUT2 regulates tau spreading via adenosinergic signaling mediated ASAP1 pathway in neurons
Xu, H. W., Qiu, Q., Hu, P., Hoxha, K., Jang, E., O’Reilly, M., Kim, C., He, Z., Marotta, N. P., Changolkar, L. N., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02703-3 · Cited by 9 · see citing works
Self-citationHyperactive neuronal networks enhance tau spread in an Alzheimer’s disease mouse modelPreprint
Barbour, A. J., Hoag, K., Cornblath, E. J., Chavez, A., Lucas, A., Li, X., Zebrowitz, S. E., Hassman, C., Vazquez, O., Xie, S. X., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.01.625514 · Cited by 6 · see citing works
Self-citationHu, M., Moloney, C. M., Przybelski, S. A., Algeciras‐Schimnich, A., Therneau, T. M., Fought, A. J., Rothberg, D. M., Nguyen, A. T., Reichard, R. R., Dickson, D. W., et al. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01852-1 · Cited by 6 · see citing works
Wang, S., Ponnusamy, M., Patel, O., Hansen, M. T., Collier, L. A., Collier, S., & Thinakaran, G. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01652-z · Cited by 6 · see citing works
Xiao, Y., Spotorno, N., An, L., Bazinet, V., Hansen, J. Y., Strandberg, O. T., Shafiei, G., Behjat, H., Funck, T., Salvadó, G., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.17.648358 · Cited by 6 · see citing works
Spontaneous pathology in PS19 tauopathy mice progresses via brain networks
Ramirez, D. M. O., Whitesell, J. D., Bhagwat, N., Thomas, T. L., Ajay, A. D., Nawaby, A., Delatour, B., Bay, S., LaFaye, P., Harris, J. A., et al. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107072 · Cited by 5 · see citing works
Li, Y., Torok, J., Zhang, S., Ding, J. L., Wang, N., Lau, C., Kulkarni, S., Anand, C., Tran, J., Cheng, M., et al. (2025) · Advanced Science · doi:10.1002/advs.202413052 · Cited by 5 · see citing works
Tsafaras, G., Cabezudo, D., Wetzels, L., Tsakogias, I., Abey, A. S., Bentea, E., Sanchiz-Calvo, M., den Haute, C. V., Wade‐Martins, R., & Baekelandt, V. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02956-6 · Cited by 5 · see citing works
Network Models of Neurodegeneration: Bridging Neuronal Dynamics and Disease Progression
Alexandersen, C. G., Brennan, G. S., Brynildsen, J. K., Henderson, M. X., Iturria‐Medina, Y., & Bassett, D. S. (2026) · IEEE Reviews in Biomedical Engineering · doi:10.1109/rbme.2025.3643310 · Cited by 7 · see citing works
Self-citationVatsa, N., Brynildsen, J. K., Goralski, T. M., Kurgat, K., Meyerdirk, L. K., Breton, E., DeWeerd, D., Brasseur, L., Turner, L., Becker, K., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.22.619411 · Cited by 5 · see citing works
Self-citationRole of LRRK2 in axonal transport and Parkinson’s disease
Twellsieck, B., & Boecker, C. A. (2025) · Biochemical Journal · doi:10.1042/bcj20253133 · Cited by 13 · see citing works
Formation of templated inclusions in a forebrain α-synuclein mouse model is independent of LRRK2
Dues, D. J., Ma, Y., Nguyen, A. P. T., Offerman, A. V., Beddows, I., & Moore, D. J. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106338 · Cited by 4 · see citing works
Brain network dynamics codify heterogeneity in seizure propagationPreprint
Rungratsameetaweemana, N., Lainscsek, C. S. M., Cash, S. S., Garcia, J. O., B, T. J. S. A., & Bansal, K. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.12.448205 · Cited by 4 · see citing works
Molecular and connectomic vulnerability shape cross-disorder cortical abnormalitiesPreprint
Hansen, J. Y., Shafiei, G., Vogel, J. W., Smart, K. A., Bearden, C. E., Hoogman, M., Franke, B., van Rooij, D., Buitelaar, J. K., McDonald, C. R., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.21.476409 · Cited by 4 · see citing works
Luan, Y., Huang, Q., Wang, J., Guan, Y., Li, B., Franzmeier, N., Xie, F., & Ewers, M. (2025) · Brain · doi:10.1093/brain/awaf425 · Cited by 3 · see citing works
Emerging directions in tauopathy research
Buée, L., Wildsmith, K. R., Alladi, S., Bertucci, T. B., Boche, D., Bowles, K. R., Boxer, A. L., Brummet, J., DeVos, S. L., Diaz, K., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71431 · Cited by 3 · see citing works
Does proteopathic tau propagate trans-synaptically in the brain?
Hu, W. H., Liu, F., Gong, C., & Iqbal, K. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00527-x · Cited by 3 · see citing works
Temporal heterogeneity shapes diffusion dynamics in complex networks
Luo, C., Lambiotte, R., & Ji, P. (2026) · Nature Communications · doi:10.1038/s41467-026-72161-w · Cited by 4 · see citing works
Data-driven simulation of network-based tau spreading tailored to individual Alzheimer's patients
Kim, S.-W., Cho, H., Lee, Y., Lyoo, C. H., Seong, J., & Initiative, A. D. N. (2024) · Engineering With Computers · doi:10.1007/s00366-024-01988-y · Cited by 2 · see citing works
Targeting Endogenous Tau in Seeded Tauopathy Models Inhibits Tau Spread
Jang, E., Hoxha, K., Mozier, D., Insana, A., Farber, E., Changolkar, L. N., Zhang, B., Chio, T. I., Crowe, A., Chen, R. J., et al. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.0877-24.2024 · Cited by 2 · see citing works
Self-citationAlzheimer’s Tau seeds-induced pathology enhances hippocampal extracellular diffusion
Estaún‐Panzano, J., Lovisotto, A., Mazzocco, C., Piva, C., Darricau, M., Calaresu, I., Gresil, Q., Planche, V., Dehay, B., Groc, L., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-09054-z · Cited by 1 · see citing works
Cardona, E. A., Webber, C. J., Wu, Z., Bolton, B., Cenik, E. S., & Pierce-Shimomura, J. T. (2026) · Disease Models & Mechanisms · doi:10.1242/dmm.052469 · Cited by 1 · see citing works
Neuronal activity and amyloid-β cause tau seeding in the entorhinal cortex in Alzheimer’s diseasePreprint
Alexandersen, C. G., Bassett, D. S., Goriely, A., Chaggar, P., & Initiative, T. A. D. N. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.07.642054 · Cited by 1 · see citing works
Self-citationBrainPainter v2: Mouse Brain Visualization SoftwarePreprint
Mallela, V., Golland, P., & Marinescu, R. V. (2021) · arXiv (Cornell University) · doi:10.48550/arxiv.2103.14696
Jiang, J., Sun, J., Xue, L., Lu, J., Zhang, Q., Zhang, S., Wang, L., Wang, M., Zuo, C., & Tian, M. (2023) · Research Square · doi:10.21203/rs.3.rs-3399187/v1
Cardona, E. A., Webber, C. J., Wu, Z., Bolton, B. M., Cenik, E. S., & Pierce, J. T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.06.652574
Wafa, M. A., Barakat, A. K., Shaheen, M., Tarif, A., Hesham, A., Elraeya, A. Y., Ata, A. H., Elkasabi, A. G., Elkaffas, M., & Esawy, A. (2025) · Research Square · doi:10.21203/rs.3.rs-8090222/v1
Lee, W. J., Cho, H., Baek, M. S., Kim, H.-K., Lee, J. H., Ryu, Y. H., Lyoo, C. H., & Seong, J.-K. (2022) · Figshare · doi:10.6084/m9.figshare.20887205
Lubben, N., Brynildsen, J. K., Webb, C. M., Li, H. L., Leyns, C. E. G., Changolkar, L. N., Zhang, B., Meymand, E. S., O’Reilly, M., Madaj, Z., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25341205
Self-citationChaggar, P., Vogel, J. W., Thompson, T., Aldea, R., Strandberg, O. T., Stomrud, E., Palmqvist, S., Ossenkoppele, R., Jbabdi, S., Magon, S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.27.701320
Influence of sex on tau distribution across Braak stages in the Alzheimer's disease spectrum
Gatto, R. G., & Youssef, H. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261433219
Alexandersen, C. G., Brynildsen, J. K., Prigent, A., Tamborrino, M., Mantziou, A., Kurgat, K., Henderson, M. X., & Bassett, D. S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.27.714785
Self-citationGonzález-Cabrero, J., Cardoso, C. G. S., Moreno‐González, I., & de Sousa, R. J. A. (2026) · Biomechanics and Modeling in Mechanobiology · doi:10.1007/s10237-026-02092-4
González-Cabrero, J., Cardoso, C. G. S., Moreno‐González, I., Edwards, G., & de Sousa, R. J. A. (2026) · Mathematics · doi:10.3390/math14132325
Experimental quality control induces changes in Allen mouse brain connectomes
Nathan, V., Tullo, S., Portillo, L. H., Devenyi, G. A., Yee, Y., & Chakravarty, M. M. (2026) · Imaging Neuroscience · doi:10.1162/imag.a.1310
- Authors
- Cornblath, E. J., Li, H. L., Changolkar, L., Zhang, B., Brown, H. J., Gathagan, R. J., Olufemi, M. F., Trojanowski, J. Q., Bassett, D. S., Lee, V. M. Y., & Henderson, M. X.
- Affiliations
- University of Pennsylvania (US)
- Institute on Aging (US)
- Santa Fe Institute (US)
- Van Andel Institute (US)
- Corresponding author
- Henderson, Michael X.
- ORCID
- Venue
- Science Advances
- Published
- 2021-06-11
- Volume
- 7
- Issue
- 24
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC8189700
- OpenAlex
- W3172351936
- Cited by
- 66
- References
- 65
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 10 · 2023: 11 · 2022: 12 · 2021: 4
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (PHY-1554488, BCS-1631550)
- National Institutes of Health (T32-AG000255, P30-AG10124, U19-AG062418, P50-NS053488, F30-MH118871, R01-NS099348)
- John D. and Catherine T. MacArthur Foundation
- Indian Statistical Institute (16879, P30-AG10124, U19-AG062418, P50-NS053488, F30 MH118871-01, PHY-1554488, BCS-1631550)
- Michael J. Fox Foundation for Parkinson’s Research (16879)
- Alfred P. Sloan Foundation
- Paul G. Allen Family Foundation
- ISI Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau pathology, Alzheimer's disease, tauopathy, neuropathological staging, regional vulnerability, connectome, diffusion modeling, LRRK2 mutations, gene expression
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
