Hierarchical Organization of Tau and Amyloid Deposits in the Cerebral Cortex
Open accessAbstract
Importance: Abnormal accumulation of tau and amyloid-β (Aβ) proteins in the human brain are 2 pathologic hallmarks of Alzheimer disease (AD). Because pathologic processes begin decades before the onset of the clinical manifestations, the study of the cortical distribution of early-stage pathologic alterations is critical in understanding the underpinnings of the disease. Objectives: To identify the in vivo brain spatial distributions of tau and Aβ deposits in a sample of cognitively normal participants in the Harvard Aging Brain Study, determine spatial patterns of pathologic alterations, and provide means for improved individual in vivo staging. Design, Setting, and Participants: Eighty-eight individuals from the general community underwent flortaucipir 18 T807 (18F-T807) and carbon 11-labeled Pittsburgh Compound B (11C-PiB) positron emission tomographic (PET) imaging. A voxel-level hierarchical clustering approach was used to obtain the main clustering partitions corresponding to the cortical distribution maps of 18F-T807 and 11C-PiB. Hierarchical relationships between areas of distinctive pathologic deposits were then studied. Using cerebellar gray reference, 18F-T807 data were expressed as standardized uptake value ratio, and 11C-PiB were given as distribution volume ratio. Main Outcomes and Measures: Main in vivo and hierarchically organized tau and Aβ deposits in the elderly brain. Results: Of the 88 study participants, 39 (44%) were men, with a mean (SD) age of 76.2 (6.2) years. The tau and Aβ maps both displayed optimal cortical partitions at 4 clusters. The tau deposits were grouped in the temporal lobe, distributed in heteromodal areas, medial and visual regions, and primary somatomotor cortex; the Aβ deposits were clustered in the heteromodal areas and rather patchy in distributed regions involving the primary cortices, medial structures, and temporal areas. Moreover, tau deposits in the temporal lobe and distributed heteromodal areas were tightly nested. Conclusions and Relevance: Tau and Aβ deposits in the elderly brain generally display well-defined hierarchical cortical relationships as well as overlaps between the principal clusters of both pathologic alterations in the heteromodal association regions. These findings represent systematic, large-scale mechanisms of early AD pathology.
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?
Amyloid plaques do not accumulate in discrete brain areas; they are relatively widespread across most regions of the neocortex, followed by the entorhinal cortex and hippocampus of Alzheimer's disease patients.
“Amyloid plaques do not accumulate in discrete brain areas. Rather, they are relatively widespread across most regions of the neocortex, followed by the entorhinal cortex and hippocampus of AD patients (Sepulcre et al., 2017; Thal et al., 2002).”
From Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis (2020) · cites this paper as Sepulcre et al., 2017
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
Silhouettes: A graphical aid to the interpretation and validation of cluster analysis
Rousseeuw, P. J. (1987) · Journal of Computational and Applied Mathematics · doi:10.1016/0377-0427(87)90125-7 · Cited by 21,392 · see citing works
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010 · 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
The organization of the human cerebral cortex estimated by intrinsic functional connectivity
Thomas Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., Roffman, J. L., Smoller, J. W., Zöllei, L., Polimeni, J. R., et al. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00338.2011 · Cited by 9,182 · see citing works
Self-citationThe organization of the human cerebellum estimated by intrinsic functional connectivity
Buckner, R. L., Krienen, F. M., Castellanos, A., Diaz, J. C., & Yeo, B. T. T. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00339.2011 · Cited by 7,304 · see citing works
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056 · see citing works
Functional connectivity in the resting brain: a network analysis of the default mode hypothesis
Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0135058100 · Cited by 6,358 · see citing works
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806 · see citing works
The brain's default mode network
Raichle, M. E. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014030 · Cited by 3,904 · see citing works
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490 · see citing works
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345 · see citing works
Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052 · see citing works
Neurodegenerative Diseases Target Large-Scale Human Brain Networks
Seeley, W. W., Crawford, R. K., Zhou, J., Miller, B. L., & Greicius, M. D. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.024 · Cited by 2,350 · see citing works
Self-propagation of pathogenic protein aggregates in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2013) · Nature · doi:10.1038/nature12481 · Cited by 1,663 · see citing works
Palop, J. J., Chin, J., Roberson, E. D., Wang, J., Thwin, M. T., Bien-Ly, N., Yoo, J., Ho, K. O., Yu, G.-Q., Kreitzer, A., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.025 · Cited by 1,653 · see citing works
Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks
Palop, J. J., & Mucke, L. (2010) · Nature Neuroscience · doi:10.1038/nn.2583 · Cited by 1,651 · see citing works
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
PET Imaging of Tau Deposition in the Aging Human Brain
Schöll, M., Lockhart, S. N., Schonhaut, D. R., O’Neil, J. P., Janabi, M., Ossenkoppele, R., Baker, S. L., Vogel, J. W., Faria, J., Schwimmer, H. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.028 · Cited by 1,214 · see citing works
A Population-Average, Landmark- and Surface-based (PALS) atlas of human cerebral cortex
Van Essen, D. C. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.06.058 · Cited by 1,151 · see citing works
[ <sup>11</sup> C]PIB in a nondemented population: Potential antecedent marker of Alzheimer disease
Mintun, M. A., LaRossa, G. N., Sheline, Y. I., Dence, C. S., Lee, S. Y., Mach, R. H., Klunk, W. E., Mathis, C. A., DeKosky, S. T., & Morris, J. C. (2006) · Neurology · doi:10.1212/01.wnl.0000228230.26044.a4 · Cited by 1,036 · see citing works
Tau positron emission tomographic imaging in aging and early <scp>A</scp> lzheimer disease
Johnson, K. A., Schultz, A., Betensky, R. A., Becker, J. A., Sepulcre, J., Rentz, D., Mormino, E., Chhatwal, J., Amariglio, R., Papp, K., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24546 · Cited by 986 · see citing works
Self-citationSynthesis and Evaluation of 11C-Labeled 6-Substituted 2-Arylbenzothiazoles as Amyloid Imaging Agents
Mathis, C. A., Wang, Y., Holt, D. P., Huang, G.-F., Debnath, M. L., & Klunk, W. E. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm030026b · Cited by 976 · see citing works
Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease
Ikonomovic, M. D., Klunk, W. E., Abrahamson, E. E., Mathis, C. A., Price, J. C., Tsopelas, N. D., Lopresti, B. J., Ziolko, S., Bi, W., Paljug, W. R., et al. (2008) · Brain · doi:10.1093/brain/awn016 · Cited by 933 · see citing works
Brain Imaging in Alzheimer Disease
Johnson, K. A., Fox, N. C., Sperling, R. A., & Klunk, W. E. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006213 · Cited by 875 · see citing works
Self-citationPrion-like mechanisms in neurodegenerative diseases
Frost, B., & Diamond, M. I. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2786 · Cited by 776 · see citing works
Maruyama, M., Shimada, H., Suhara, T., Shinotoh, H., Ji, B., Maeda, J., Zhang, M.-R., Trojanowski, J. Q., Lee, V. M.-Y., Ono, M., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.037 · Cited by 760 · see citing works
A 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
Evolution of the neuropathology of Alzheimer's disease
Braak, H., & Braak, E. (1996) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1996.tb05866.x · Cited by 710 · see citing works
Predicting Regional Neurodegeneration from the Healthy Brain Functional Connectome
Zhou, J., Gennatas, E. D., Kramer, J. H., Miller, B. L., & Seeley, W. W. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.004 · Cited by 706 · see citing works
Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F18]-T808
Chien, D. T., Szardenings, A. K., Bahri, S., Walsh, J. C., Mu, F., Xia, C. A., Shankle, W. R., Lerner, A. J., Su, M., Elizarov, A. M., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130098 · Cited by 676 · see citing works
Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807
Chien, D. T., Bahri, S., Szardenings, A. K., Walsh, J. C., Mu, F., Su, M.-Y., Shankle, W. R., Elizarov, A., & Kolb, H. C. (2013) · Journal of Alzheimer's Disease · doi:10.3233/jad-122059 · Cited by 651 · see citing works
Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections
Braak, H., & Braak, E. (1991) · Brain Pathology · doi:10.1111/j.1750-3639.1991.tb00661.x · Cited by 598 · see citing works
Clinical Gerontology: A Guide to Assessment and Intervention
Brink, T. L. (1986) · Medical Entomology and Zoology · Cited by 592 · see citing works
Lopresti, B. J., Klunk, W. E., Mathis, C. A., Hoge, J. A., Ziolko, S. K., Lu, X., MELTZER, C. C., Schimmel, K., Tsopelas, N. D., DeKosky, S. T., et al. (2005) · PubMed · Cited by 536 · see citing works
Resting state functional connectivity in preclinical Alzheimer’s disease
Sheline, Y. I., & Raichle, M. E. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.11.028 · Cited by 509 · see citing works
In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum
Cho, H., Choi, J. Y., Hwang, M. S., Kim, Y. J., Lee, H. M., Lee, H. S., Lee, J. H., Ryu, Y. H., Lee, M. S., & Lyoo, C. H. (2016) · Annals of Neurology · doi:10.1002/ana.24711 · Cited by 499 · see citing works
Morris, J. C., Edland, S., Clark, C., Galasko, D., Koss, E., Mohs, R., van Belle, G., Fillenbaum, G., & Heyman, A. (1993) · Neurology · doi:10.1212/wnl.43.12.2457 · Cited by 441 · see citing works
Oligomers on the Brain: the Emerging Role of Soluble Protein Aggregates in Neurodegeneration.
Walsh, D. M., & Selkoe, D. J. (2004) · Protein and Peptide Letters · doi:10.2174/0929866043407174 · Cited by 428 · see citing works
Amyloid‐β associated cortical thinning in clinically normal elderly
Becker, J. A., Hedden, T., Carmasin, J., Maye, J., Rentz, D. M., Putcha, D., Fischl, B., Greve, D. N., Marshall, G. A., Salloway, S., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22333 · Cited by 342 · see citing works
Self-citationOkamura, N., Furumoto, S., Harada, R., Tago, T., Yoshikawa, T., Fodero‐Tavoletti, M. T., Mulligan, R. S., Villemagne, V. L., Akatsu, H., Yamamoto, T., et al. (2013) · Journal of Nuclear Medicine · doi:10.2967/jnumed.112.117341 · Cited by 289 · see citing works
Ogomori, K., Kitamoto, T., Tateishi, J., Sato, Y., Suetsugu, M., & Abe, M. (1989) · Europe PMC (PubMed Central) · Cited by 245 · see citing works
Villain, N., Fouquet, M., Baron, J.-C., Mezenge, F., Landeau, B., de La Sayette, V., Viader, F., Eustache, F., Desgranges, B., & Chetelat, G. (2010) · Brain · doi:10.1093/brain/awq203 · Cited by 237 · see citing works
WHITE MATTER CHANGES IN DEMENTIA OF ALZHEIMER'S TYPE: BIOCHEMICAL AND NEUROPATHOLOGICAL CORRELATES
ENGLUND, E., BRUN, A., & ALLING, C. (1988) · Brain · doi:10.1093/brain/111.6.1425 · Cited by 228 · see citing works
In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain
Sepulcre, J., Schultz, A. P., Sabuncu, M. R., Gómez‐Isla, T., Chhatwal, J. P., Becker, A., Sperling, R. A., & Johnson, K. A. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0639-16.2016 · Cited by 173 · see citing works
Self-citationIn vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease
Villemagne, V. L., Furumoto, S., Fodero‐Tavoletti, M. T., Mulligan, R. S., Hodges, J. R., Harada, R., Yates, P. A., Piguet, O., Pejoska, S., Doré, V., et al. (2014) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-013-2681-7 · Cited by 170 · see citing works
The role of extracellular Tau in the spreading of neurofibrillary pathology
Medina, M., & Avila, J. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00113 · Cited by 161 · see citing works
Vulnerability of Select Neuronal Types to Alzheimer's Disease
BRAAK, H., DEL TREDICI, K., SCHULTZ, C., & BRAAK, E. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb05560.x · Cited by 150 · see citing works
Vlassenko, A. G., Mintun, M. A., Xiong, C., Sheline, Y. I., Goate, A., Benzinger, T. L. S., & Morris, J. C. (2011) · Annals of Neurology · doi:10.1002/ana.22608 · Cited by 144 · see citing works
In vivo characterization of the early states of the amyloid-beta network
Sepulcre, J., Sabuncu, M. R., Becker, A., Sperling, R., & Johnson, K. A. (2013) · Brain · doi:10.1093/brain/awt146 · Cited by 117 · see citing works
Self-citationSpatial patterns of brain amyloid- burden and atrophy rate associations in mild cognitive impairment
Tosun, D., Schuff, N. W., Mathis, C. A., Jagust, W., Weiner, M. W., & Initiative, A. D. N. (2011) · Brain · doi:10.1093/brain/awr044 · Cited by 117 · see citing works
Teipel, S. J., Grothe, M. J., Zhou, J. H., Sepulcre, J., Dyrba, M., Sorg, C., & Babiloni, C. (2016) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617715000995 · Cited by 115 · see citing works
Self-citationSojkova, J., Driscoll, I. F., Iacono, D., Zhou, Y., Codispoti, K.-E., Kraut, M. A., Ferrucci, L., Pletniková, O., Mathis, C. A., Klunk, W. E., et al. (2011) · Archives of Neurology · doi:10.1001/archneurol.2010.357 · Cited by 112 · see citing works
White matter integrity and cortical metabolic associations in aging and dementia
Kuczynski, B., Targan, E., Madison, C. M., Weiner, M. W., Zhang, Y., Reed, B., Chui, H. C., & Jagust, W. J. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2009.04.1228 · Cited by 56 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Johnson K, Becker AJ, Sepulcre J, et al. Tau PET imaging in aging and early Alzheimer's disease. Ann Neurol. 2016;79(1):110-119.
- C]PIBin a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006;67(3):446-452.
Cited by
Sorted by citations
Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606 · see citing works
Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study
Hanseeuw, B. J., Betensky, R. A., Jacobs, H. I. L., Schultz, A. P., Sepulcre, J., Becker, J. A., Cosio, D. M. O., Farrell, M., Quiroz, Y. T., Mormino, E. C., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.1424 · Cited by 865 · see citing works
Self-citationLongitudinal tau PET in ageing and Alzheimer’s disease
Jack, C. R., Wiste, H. J., Schwarz, C. G., Lowe, V. J., Senjem, M. L., Vemuri, P., Weigand, S. D., Therneau, T. M., Knopman, D. S., Gunter, J. L., et al. (2018) · Brain · doi:10.1093/brain/awy059 · Cited by 452 · see citing works
Preventing dementia by preventing stroke: The Berlin Manifesto
Hachinski, V., Einhäupl, K. M., Ganten, D., Alladi, S., Brayne, C., Stephan, B. C. M., Sweeney, M. D., Zloković, B. V., Iturria‐Medina, Y., Iadecola, C., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.06.001 · Cited by 314 · see citing works
A walk through tau therapeutic strategies
Jadhav, S., Ávila, J., Schöll, M., Kovács, G. G., Kövari, E., Škrabana, R., Evans, L., Kontseková, E., Malawska, B., de Silva, R., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0664-z · Cited by 286 · see citing works
Functional connectivity associated with tau levels in ageing, Alzheimer’s, and small vessel disease
Franzmeier, N., Rubinski, A., Neitzel, J., Kim, Y., Damm, A., Na, D. L., Kim, H. J., Lyoo, C. H., Cho, H., Finsterwalder, S., et al. (2019) · Brain · doi:10.1093/brain/awz026 · Cited by 234 · see citing works
Schöll, M., Maaß, A., Mattsson, N., Ashton, N. J., Blennow, K., Zetterberg, H., & Jagust, W. J. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.12.001 · Cited by 227 · see citing works
Mirzaei, G., & Adeli, H. (2021) · Biomedical Signal Processing and Control · doi:10.1016/j.bspc.2021.103293 · Cited by 214 · see citing works
Neurogenetic contributions to amyloid beta and tau spreading in the human cortex
Sepulcre, J., Grothe, M. J., Uquillas, F. D., Ortiz-Terán, L., Diez, I. P., Yang, H., Jacobs, H. I. L., Hanseeuw, B. J., Li, Q., Fakhri, G. E., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0206-4 · Cited by 190 · see citing works
Self-citationSelective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis
Roussarie, J.-P., Yao, V., Rodriguez-Rodriguez, P., Oughtred, R., Rust, J., Plautz, Z., Kasturia, S., Albornoz, C., Wang, W., Schmidt, E. F., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.010 · Cited by 180 · see citing works
Clinical Research on Alzheimer’s Disease: Progress and Perspectives
Sun, B., Li, W., Zhu, C., Jin, W., Zeng, F., Liu, Y.-H., Bu, X., Zhu, J., Yao, X., & Wang, Y. (2018) · Neuroscience Bulletin · doi:10.1007/s12264-018-0249-z · Cited by 164 · see citing works
Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology
Grothe, M. J., Sepulcre, J., Gonzalez-Escamilla, G., Jelistratova, I., Schöll, M., Hansson, O., Teipel, S. J., & Initiative, A. D. N. (2018) · Brain · doi:10.1093/brain/awy189 · Cited by 142 · see citing works
Self-citationPereira, J. B., Ossenkoppele, R., Palmqvist, S., Strandberg, T. O., Smith, R. A., Westman, E., & Hansson, O. (2019) · eLife · doi:10.7554/elife.50830 · Cited by 91 · see citing works
Molecular imaging in dementia: Past, present, and future
Laforce, R. J., Soucy, J., Sellami, L., Dallaire‐Théroux, C., Brunet, F., Bergeron, D., Miller, B. L., & Ossenkoppele, R. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.06.2855 · Cited by 87 · see citing works
The Role of Genetics in Advancing Precision Medicine for Alzheimer’s Disease—A Narrative Review
Freudenberg‐Hua, Y., Li, W., & Davies, P. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00108 · Cited by 74 · see citing works
Anti-Tau Trials for Alzheimer's Disease: A Report from the EU/US/CTAD Task Force
Cummings, J. L., Blennow, K., Johnson, K. A., Keeley, M. B., Bateman, R. J., Molinuevo, J. L., Touchon, J., Aisen, P. S. S., & Vellas, B. J. (2019) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2019.14 · Cited by 71 · see citing works
Self-citationFurcila, D., DeFelipe, J., & Alonso‐Nanclares, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180173 · Cited by 70 · see citing works
Leerssen, J., Blanken, T. F., Pozzi, E., Jahanshad, N., Aftanas, L. I., Andreassen, O. A., Baune, B. T., Brack, I., Carballedo, A., Ching, C. R. K., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-01109-5 · Cited by 63 · see citing works
Amyloid-β: A double agent in Alzheimer's disease?
Yu, H., & Wu, J. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111575 · Cited by 62 · see citing works
Alzheimer's disease neuroimaging
Whitwell, J. L. (2018) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000570 · Cited by 64 · see citing works
Rodriguez‐Vieitez, E., Montal, V., Sepulcre, J., Lois, C., Hanseeuw, B. J., Vilaplana, E., Schultz, A. P., Properzi, M. J., Scott, M. R., Amariglio, R. E., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01290-z · Cited by 47 · see citing works
Self-citationDuong, M. T., Das, S. R., Lyu, X., Xie, L., Richardson, H., Xie, S. X., Yushkevich, P. A., Initiative, A. D. N., Weiner, M. W., Aisen, P. S. S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28941-1 · Cited by 44 · see citing works
Self-citationCastrillo, J. I., Lista, S., Hampel, H. J., & Ritchie, C. W. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7704-8_3 · Cited by 44 · see citing works
Data‐driven approaches for tau‐PET imaging biomarkers in Alzheimer's disease
Vogel, J. W., Mattsson, N., Iturria‐Medina, Y., Strandberg, O. T., Schöll, M., Dansereau, C. L., Villeneuve, S., van der Flier, W. M., Scheltens, P., Bellec, P., et al. (2018) · Human Brain Mapping · doi:10.1002/hbm.24401 · Cited by 41 · see citing works
Pereira, J. B., Harrison, T. M., Joie, R. L., Baker, S. L., & Jagust, W. J. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04669-x · Cited by 39 · see citing works
The Pathoconnectivity Profile of Alzheimer’s Disease: A Morphometric Coalteration Network Analysis
Manuello, J., Nani, A., Premi, E., Borroni, B., Costa, T., Tatu, K., Liloia, D., Duca, S., & Cauda, F. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2017.00739 · Cited by 37 · see citing works
Global brain activity and its coupling with cerebrospinal fluid flow is related to tau pathology
Han, F., Lee, J., Chen, X., Ziontz, J., Ward, T. J., Landau, S. M., Baker, S. L., Harrison, T. M., Jagust, W. J., & Initiative, A. D. N. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14296 · Cited by 42 · see citing works
Heterotypic interactions in amyloid function and disease
Konstantoulea, K., Louros, N. N., Rousseau, F., & Schymkowitz, J. W. H. (2021) · FEBS Journal · doi:10.1111/febs.15719 · Cited by 32 · see citing works
Selective neuronal vulnerability in Alzheimer’s disease: a network-based analysisPreprint
Roussarie, J.-P., Yao, V., Plautz, Z., Kasturia, S. E., Albornoz, C. A., Schmidt, E. F., Brichta, L., Barnea-Cramer, A. O., Heintz, N., Hof, P. R., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/499897 · Cited by 31 · see citing works
Hachinski, V., Einhäupl, K. M., Ganten, D., Alladi, S., Brayne, C., Stephan, B. C. M., Sweeney, M. D., Zloković, B. V., Iturria‐Medina, Y., Iadecola, C., et al. (2019) · International Journal of Stroke · doi:10.1177/1747493019871915 · Cited by 28 · see citing works
Recent Developments in Positron Emission Tomography Tracers for Proteinopathies Imaging in Dementia
Ni, R., & Nitsch, R. M. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.751897 · Cited by 29 · see citing works
Louros, N., Ramakers, M., Michiels, E., Konstantoulea, K., Morelli, C., Garcia, T., Moonen, N., D’Haeyer, S., Goossens, V., Thal, D. R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28955-9 · Cited by 28 · see citing works
Burnham, S. C., Iaccarino, L., Pontecorvo, M. J., Fleisher, A., Lu, M., Collins, E. C., & Devous, M. D. (2023) · Brain Communications · doi:10.1093/braincomms/fcad305 · Cited by 29 · see citing works
Longitudinal predictive modeling of tau progression along the structural connectome
Yang, F., Chowdhury, S. R., Jacobs, H. I. L., Sepulcre, J., Wedeen, V. J., Johnson, K. A., & Dutta, J. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118126 · Cited by 22 · see citing works
Self-citationAmyloid‐β in Alzheimer's disease: Structure, toxicity, distribution, treatment, and prospects
Yu, Y., Yu, S., Battaglia, G., & Tian, X. (2024) · Ibrain · doi:10.1002/ibra.12155 · Cited by 19 · see citing works
Recent Advances in Imaging of Preclinical, Sporadic, and Autosomal Dominant Alzheimer's Disease
Buckley, R. F. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01026-5 · Cited by 18 · see citing works
Data‐driven decomposition and staging of flortaucipir uptake in Alzheimer's disease
Earnest, T., Bani, A., Ha, S. M., Hobbs, D. A., Kothapalli, D., Yang, B., Lee, J. J., Benzinger, T. L. S., Gordon, B. A., Sotiras, A., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13769 · Cited by 17 · see citing works
Hypometabolic mismatch with atrophy and tau pathology in mixed Alzheimer’s and Lewy body disease
Duong, M. T., Das, S. R., Khandelwal, P., Lyu, X., Xie, L., McGrew, E., Dehghani, N., McMillan, C. T., Lee, E. B., Shaw, L. M. J., et al. (2024) · Brain · doi:10.1093/brain/awae352 · Cited by 17 · see citing works
Distance disintegration delineates the brain connectivity failure of Alzheimer's disease
Costumero, V., Uquillas, F. D., Diez, I. P., Andorrà, M., Basaia, S., Bueichekú, E., Ortiz-Terán, L., Belloch, V., Escudero, J. V., Ávila, C., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.12.005 · Cited by 16 · see citing works
Self-citationTürker, F., Bharadwaj, R. A., Kleinman, J. E., Weinberger, D. R., Hyde, T. M., White, C. J., Williams, D. W., & Margolis, S. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104811 · Cited by 16 · see citing works
Relationship between comprehensive geriatric assessment and amyloid PET in older persons with MCI
Lauretani, F., Ruffini, L., Scarlattei, M., & Maggio, M. G. (2020) · BMC Geriatrics · doi:10.1186/s12877-020-01746-x · Cited by 16 · see citing works
Qiao, Z., Wang, G., Zhao, X. B., Wang, K., Fan, D., Chen, Q., & Ai, L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.841942 · Cited by 15 · see citing works
Long non‐coding RNAs as key regulators of neurodegenerative protein aggregation
Xu, Q., Liu, D., Zhu, L., Su, Y., & Huang, H. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14498 · Cited by 15 · see citing works
Dose-dependent phosphorylation of endogenous Tau by intermittent hypoxia in rat brain
Marciante, A. B., Howard, J. C., Kelly, M. N., Santiago‐Moreno, J., Allen, L. L., Gonzalez‐Rothi, E. J., & Mitchell, G. S. (2022) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00332.2022 · Cited by 15 · see citing works
Spatial extent as a sensitive amyloid‐PET metric in preclinical Alzheimer's disease
Farrell, M. E., Thibault, E. G., Becker, J. A., Price, J. C., Healy, B. C., Hanseeuw, B. J., Buckley, R. F., Jacobs, H. I. L., Schultz, A. P., Chen, C. D., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14036 · Cited by 13 · see citing works
Self-citationAssociation of tau accumulation and atrophy in mild cognitive impairment: a longitudinal study
Xu, G., Zheng, S., Zhu, Z., Yu, X., Jiang, J. C., Jiang, J., Chu, Z., & Initiative, A. D. N. (2020) · Annals of Nuclear Medicine · doi:10.1007/s12149-020-01506-2 · Cited by 12 · see citing works
Tau Diagnostics and Clinical Studies
Gozes, I., Höglinger, G. U., Quinn, J. P., Hooper, N. M., & Höglund, K. (2017) · Journal of Molecular Neuroscience · doi:10.1007/s12031-017-0983-0 · Cited by 12 · see citing works
Functional brain network architecture may route progression of Alzheimer’s disease pathology
Franzmeier, N., & Dyrba, M. (2017) · Brain · doi:10.1093/brain/awx304 · Cited by 11 · see citing works
Shao, Z., Gao, X., Cen, S., Tang, X., Gong, J., & Ding, W. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.08.094 · Cited by 9 · see citing works
Linking Amyloid-β and Tau Deposition in Alzheimer Disease
Vemuri, P., & Schöll, M. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.0323 · Cited by 9 · see citing works
Computational modelling of pathogenic protein spread in neurodegenerative diseases
Georgiadis, K. L., Wray, S., Sebastien Ourselin, A., Warren, J. D., & Marc Modat, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0192518 · Cited by 9 · see citing works
Shepherd, A. L., Lim, J. K. H., Wong, V. H. Y., Zeleznikow-Johnston, A., Churilov, L. P., Nguyen, C. T. O., Bui, B. V., Hannan, A. J., & Burrows, E. L. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.08.004 · Cited by 8 · see citing works
Hayden, E. Y., Huang, J., Charreton, M., Nuñez, S., Putman, J. N., Teter, B., Lee, J. T., Welch, A. E., Frautschy, S. A., Cole, G. M., et al. (2020) · Translational Stroke Research · doi:10.1007/s12975-020-00786-0 · Cited by 7 · see citing works
Amyloid‐β but not tau accumulation is strongly associated with longitudinal cognitive decline
Wang, W., Huang, J., Qian, S., Zheng, Y., Yu, X., Jiang, T., Ai, R., Hou, J., Ma, E., Cai, J., et al. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14860 · Cited by 5 · see citing works
Kim, J., Kim, S., Um, Y. H., Wang, S., Kim, R. E. Y., Choe, Y. S., Lee, J., Kim, D., Lim, H. K., Lee, C. U., et al. (2023) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.23.1113 · Cited by 5 · see citing works
Brain Network Functional Connectivity in Alzheimer’s Disease and Frontotemporal Dementia
Zhou, J. H., Ng, K. K., & Liu, S. (2020) · Springer eBooks · doi:10.1007/978-3-030-41874-8_25 · Cited by 4 · see citing works
Speech Registration in Symptomatic Memory Impairment
Kamourieh, S., Braga, R. M., Leech, R., Mehta, A., & Wise, R. G. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00201 · Cited by 4 · see citing works
De "perfecta casada" a "ángel del hogar" o la construcción del arquetipo femenino en el siglo XIX
Rosales, C., & Ángeles, M. D. L. (2007) · Hispana · Cited by 4 · see citing works
Patterns of pathological tau deposition reflect the dynamics of cortical brain activity
Han, F., Chen, X., Murphy, A., Lee, J., Ziontz, J., Landau, S. M., Baker, S. L., Harrison, T. M., & Jagust, W. J. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115853 · Cited by 3 · see citing works
An evaluation of the amyloid cascade model using in vivo positron emission tomographic imaging
Yasuno, F., Nakamura, A., Kato, T., Iwata, K., Sakurai, T., Arahata, Y., Washimi, Y., Hattori, H., & Ito, K. (2020) · Psychogeriatrics · doi:10.1111/psyg.12589 · Cited by 3 · see citing works
Vlegels, N., Ossenkoppele, R., van der Flier, W. M., Koek, H. L., Reijmer, Y. D., Wisse, L. E. M., Biessels, G. J., & Initiative, T. A. D. N. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220024 · Cited by 3 · see citing works
Data-driven approaches for Tau-PET imaging biomarkers in Alzheimer’s diseasePreprint
Vogel, J. W., Mattsson, N., Iturria‐Medina, Y., Strandberg, T. O., Schöll, M., Dansereau, C. L., Villeneuve, S., van der Flier, W. M., Scheltens, P., Bellec, P., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/244574 · Cited by 3 · see citing works
Mak, E., Przybelski, S. A., Reid, R. I., Wiste, H. J., Fought, A. J., Schwarz, C. G., Senjem, M. L., Vemuri, P., Jack, C. R., Lowe, V. J., et al. (2026) · Alzheimer s Research & Therapy · doi:10.1186/s13195-026-01995-9 · Cited by 2 · see citing works
Trajectories of late-life depression: insights from molecular imaging
Holmes, S. E., & Smith, G. S. (2026) · Neuropsychopharmacology · doi:10.1038/s41386-026-02340-2 · Cited by 2 · see citing works
Hierarchical organization of the forebrain cholinergic system in rats
Varsanyi, P., Alloway, K. D., Chavez, C. M., Gielow, M. R., Gombkötő, P., Kondo, H., Nádasdy, Z., & Záborszky, L. (2025) · iScience · doi:10.1016/j.isci.2025.112001 · Cited by 3 · see citing works
Kimura, Y., Kato, T., Ito, K., & Ichise, M. (2020) · Springer eBooks · doi:10.1007/978-3-030-39457-8_4 · Cited by 2 · see citing works
Amyloid spatial extent with florbetapir-PET for early detection of preclinical Alzheimer’s disease
Thibault, E. G., Montenegro, G. A. D. C., Becker, J. A., Price, J. C., Healy, B. C., Hanseeuw, B. J., Buckley, R. F., Jacobs, H. I. L., Properzi, M. J., Sperling, R. A., et al. (2026) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2026.100529 · Cited by 1 · see citing works
Self-citationZhou, D.-A., Xu, K., Zhao, X. B., Chen, Q., Sang, F., Fan, D., Su, L., Zhang, Z., Ai, L., & Chen, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.788567 · Cited by 1 · see citing works
Functional architecture of the forebrain cholinergic system in rodentsPreprint
Záborszky, L., Varsanyi, P., Alloway, K. D., Chavez, C. M., Gielow, M. R., Gombkötő, P., Kondo, H., & Nádasdy, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-4504727/v1 · Cited by 1 · see citing works
Spatial association between distributed β-amyloid and tau varies with cognitionPreprint
Carbonell, F., McNicoll, C., Zijdenbos, A. P., Bedell, B. J., & Initiative, A. D. N. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.27.559737
da Silva, M.-N. M., James-Galton, M., Green, C. K., & Plant, G. T. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1759440
Adsit, L. M., Cekada, K., & Smith, I. T. (2026) · iScience · doi:10.1016/j.isci.2026.117187
- Authors
- Sepulcre, J., Grothe, M. J., Sabuncu, M., Chhatwal, J., Schultz, A. P., Hanseeuw, B., El Fakhri, G., Sperling, R., & Johnson, K. A.
- Affiliations
- Harvard University (US)
- German Center for Neurodegenerative Diseases (DE)
- Athinoula A. Martinos Center for Biomedical Imaging (US)
- Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Brigham and Women's Hospital (US)
- Corresponding author
- Sepulcre, Jorge
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2017-07-01
- Volume
- 74
- Issue
- 7
- Pages
- 813
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC5710537
- OpenAlex
- W2619717932
- Cited by
- 73
- References
- 54
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 9 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 9 · 2019: 8 · 2018: 16 · 2017: 3
- FWCI
- 8.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Alzheimer's Association (ZEN-10-174210)
- National Institute on Aging (K24AG035007, P01AG036694)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- amyloid-beta deposition, Alzheimer's disease, cerebral cortex, hierarchical clustering, flortaucipir PET, Pittsburgh compound B PET, temporal lobe, cognitively normal elderly
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Aniline Compounds, Cerebral Cortex, Cross-Sectional Studies, Female, Fluorine Radioisotopes, Humans, Male, Thiazoles, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Benzothiazoles
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
