Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition.
Open accessAbstract
The advent of tau-targeted positron emission tomography tracers such as flortaucipir (18F-AV-1451, also known as 18F-T807) have made it possible to investigate the sequence of development of tau and amyloid-β in relationship to age, and to the development of cognitive impairment due to Alzheimer's disease. In this study, flortaucipir tau and florbetapir amyloid positron emission tomography were obtained for 217 subjects including 16 young and 58 older cognitively normal subjects, 95 subjects with mild cognitive impairment (Mini-Mental State Examination 24-30) and 48 subjects with clinically-defined possible or probable Alzheimer's disease (Mini-Mental State Examination >10). Images were evaluated visually and quantitatively by regional and voxel-based cortical to cerebellar standard uptake value ratios. For amyloid positron emission tomography positive (Aβ+) subjects, flortaucipir neocortical standard uptake value ratio was significantly higher with more advanced clinical stage (Alzheimer's disease > mild cognitive impairment > older cognitively normal) and was significantly elevated for Aβ+ mild cognitive impairment and Alzheimer's disease subjects relative to the respective Aβ- subjects. In contrast, florbetapir Aβ- older cognitively normal subjects showed an increase in flortaucipir standard uptake value ratios in mesial temporal lobe regions (amygdala, hippocampus/choroid plexus region of interest) compared to younger cognitively normal subjects, but no increased standard uptake value ratios in neocortical regions. Analysis of covariance with planned contrasts showed no differences in regional or composite posterior neocortical flortaucipir standard uptake value ratio as a function of diagnostic group among Aβ- older cognitively normal or clinically diagnosed Alzheimer's disease or mild cognitive impairment subjects. The pattern of flortaucipir distribution among Aβ+ subjects was reminiscent of the cross-sectional distribution of tau reported in post-mortem pathology studies, in that the most commonly affected regions were the inferior and lateral temporal lobes, the same regions where the first signs of increased retention appeared in Aβ+ cognitively normal subjects. However, there was large variability in extent/density of flortaucipir tau binding among Aβ+ subjects. Although high neocortical flortaucipir retention was consistently associated with an Aβ+ florbetapir positron emission tomography scan, not all Aβ+ subjects had elevated flortaucipir standard uptake value ratios. Finally, within the Aβ+ group, increasing levels of flortaucipir tau binding were associated with increased cognitive impairment, as assessed by Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. These results suggest development of tau beyond the mesial temporal lobe is associated with, and may be dependent on, amyloid accumulation. Further, the results are consistent with the hypothesis that cortical tau is associated with cognitive impairment.
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?
Tau pathology usually occurs downstream from deposition of Aβ plaques.
“while tau pathology usually occurs downstream from the deposition of Aβ plaques.31”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [31]
The Introduction describes tau pathology appearing after amyloid-β plaques as a hypothesis, but also presents evidence that the two pathologies may begin independently. The Discussion says the results are consistent with independent beginnings and a possible dependence on amyloid for tau's later spread. The source therefore does not establish that tau pathology usually begins downstream of plaque deposition. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFlortaucipir is being developed as a positron emission tomography tracer for detection of the aggregated tau of Alzheimer disease.
“Flortaucipir is being developed as a PET tracer for detection of the aggregated tau of AD.19,21,22,23,24”
From Positron Emission Tomography Imaging With [ <sup>18</sup> F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [23]
These results are consistent with previously observed correspondence between elevated flortaucipir PET signal and elevated signal on amyloid PET.
“These results are consistent with previously observed correspondence between elevated flortaucipir PET signal and elevated signal on amyloid PET.23,45”
From Positron Emission Tomography Imaging With [ <sup>18</sup> F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [23]
Approximately 20% (19%-23%) of participants with positive amyloid PET scans have no or low levels of flortaucipir binding by quantitative or visual interpretation.
“Similarly, approximately 20% (19%-23%) of participants with positive amyloid PET scans have no or low levels of [18F]flortaucipir binding by quantitative or visual interpretation.21,23,50,51,52”
From Positron Emission Tomography Imaging With [ <sup>18</sup> F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [23]
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
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 6× · see citing works
“However, both histopathology studies in autopsy tissue (Braak and Braak, 1991) and recent PET imaging studies with amyloid and tau tracers (Brier et al., 2016; Cho et al., 2016a; Schöll et al., 2016) suggest an incomplete overlap in the pattern of distribution of amyloid and Alzheimer’s disease.”
BackgroundResultInfluentialThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155 · 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
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569 · see citing works
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431 · see citing works
Jack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., Wiste, H. J., Weigand, S. D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70291-0 · Cited by 4,396 · see citing works
Statistical Parametric Mapping: The Analysis of Functional Brain Images
Penny, W. D., Friston, K. J., Ashburner, J., Kiebel, S. J., & Thomas, N. (2007) · UCL Discovery (University College London) · Cited by 3,339 · 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
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
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708 · see citing works
Unbiased nonlinear average age-appropriate brain templates from birth to adulthood
Fonov, V., Evans, A., McKinstry, R. C., Almli, C. R., & Collins, D. L. (2009) · NeuroImage · doi:10.1016/s1053-8119(09)70884-5 · Cited by 2,092 · see citing works
Observations on the brains of demented old people
Tomlinson, B. E., Blessed, G., & Roth, M. (1970) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(70)90063-8 · Cited by 2,084 · see citing works
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611 · see citing works
Primary age-related tauopathy (PART): a common pathology associated with human aging
Crary, J. F., Trojanowski, J. Q., Schneider, J. A., Abisambra, J. F., Abner, E. L., Alafuzoff, I., Arnold, S. E., Attems, J., Beach, T. G., Bigio, E. H., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1349-0 · Cited by 1,467 · 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
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease
Ossenkoppele, R., Schonhaut, D. R., Schöll, M., Lockhart, S. N., Ayakta, N., Baker, S. L., O’Neil, J. P., Janabi, M., Lazaris, A., Cantwell, A., et al. (2016) · Brain · doi:10.1093/brain/aww027 · Cited by 1,185 · see citing works
Goedert, M., Spillantini, M. G., Cairns, N. J., & Crowther, R. A. (1992) · Neuron · doi:10.1016/0896-6273(92)90117-v · Cited by 1,114 · see citing works
Paired Helical Filaments in Electron Microscopy of Alzheimer's Disease
KIDD, M. (1963) · Nature · doi:10.1038/197192b0 · Cited by 1,012 · 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
Murray, M. E., Graff-Radford, N. R., Ross, O. A., Petersen, R. C., Duara, R., & Dickson, D. W. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70156-9 · Cited by 972 · see citing works
Clark, C. M., Pontecorvo, M. J., Beach, T. G., Bedell, B. J., Coleman, R. E., Doraiswamy, P. M., Fleisher, A. S., Reiman, E. M., Sabbagh, M. N., Sadowsky, C. H., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70142-4 · Cited by 855 · see citing works
Self-citationMaruyama, 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
Therapeutics of Alzheimer's disease: Past, present and future
Anand, R., Gill, K. D., & Mahdi, A. A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.07.004 · Cited by 748 · see citing works
Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease
Brier, M. R., Gordon, B., Friedrichsen, K., McCarthy, J., Stern, A., Christensen, J., Owen, C., Aldea, P., Su, Y., Hassenstab, J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf2362 · Cited by 734 · 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
Marquié, M., Normandin, M. D., Vanderburg, C. R., Costantino, I. M., Bien, E. A., Rycyna, L. G., Klunk, W. E., Mathis, C. A., Ikonomovic, M. D., Debnath, M. L., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24517 · Cited by 615 · see citing works
Xia, C., Arteaga, J., Chen, G., Gangadharmath, U., Gomez, L. F., Kasi, D., Lam, C., Liang, Q., Liu, C., Mocharla, V. P., et al. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2012.11.008 · Cited by 605 · see citing works
Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study
Sabri, O., Sabbagh, M. N., Seibyl, J., Barthel, H., Akatsu, H., Ouchi, Y., Senda, K., Murayama, S., Ishii, K., Takao, M., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.02.004 · Cited by 602 · see citing works
Yanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · 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
Alzheimer disease therapy—moving from amyloid-β to tau
Giacobini, E., & Gold, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.223 · Cited by 483 · see citing works
An autoradiographic evaluation of AV-1451 Tau PET in dementia
Lowe, V. J., Curran, G., Fang, P., Liesinger, A. M., Josephs, K. A., Parisi, J. E., Kantarci, K., Boeve, B. F., Pandey, M. K., Bruinsma, T., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0315-6 · Cited by 474 · see citing works
Schwarz, A. J., Yu, P., Miller, B. B., Shcherbinin, S., Dickson, J., Navitsky, M., Joshi, A. D., Devous, M. D., & Mintun, M. S. (2016) · Brain · doi:10.1093/brain/aww023 · Cited by 425 · see citing works
Self-citationRiley, K. P., Snowdon, D. A., & Markesbery, W. R. (2002) · Annals of Neurology · doi:10.1002/ana.10161 · Cited by 392 · see citing works
Curtis, C., Gamez, J. E., Singh, U., Sadowsky, C. H., Villena, T., Sabbagh, M. N., Beach, T. G., Duara, R., Fleisher, A. S., Frey, K. A., et al. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2014.4144 · Cited by 332 · see citing works
Self-citationTreatment of Alzheimer's Disease with the GSK-3 Inhibitor Tideglusib: A Pilot Study
del Ser, T., Steinwachs, K. C., Gertz, H. J., Andrés, M. V., Gómez-Carrillo, B., Medina, M., Vericat, J. A., Redondo, P., Fleet, D., & León, T. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-120805 · Cited by 329 · see citing works
Nelson, P. T., Jicha, G. A., Schmitt, F. A., Liu, H., Davis, D. G., Mendiondo, M. S., Abner, E. L., & Markesbery, W. R. (2007) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/nen.0b013e31815c5efb · Cited by 292 · see citing works
Okamura, 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
Bolmont, T., Clavaguera, F., Meyer-Luehmann, M., Herzig, M. C., Radde, R., Staufenbiel, M., Lewis, J., Hutton, M., Tolnay, M., & Jucker, M. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070403 · Cited by 281 · see citing works
Bouras, C., Hof, P. R., Giannakopoulos, P., Michel, J.-P., & Morrison, J. H. (1994) · Cerebral Cortex · doi:10.1093/cercor/4.2.138 · Cited by 280 · see citing works
Tau PET in Alzheimer disease and mild cognitive impairment
Cho, H., Choi, J. Y., Hwang, M. S., Lee, J., Kim, Y. J., Lee, H., Lyoo, C. H., Ryu, Y. H., & Lee, M. S. (2016) · Neurology · doi:10.1212/wnl.0000000000002892 · Cited by 267 · see citing works
Non-invasive assessment of Alzheimer’s disease neurofibrillary pathology using 18F-THK5105 PET
Okamura, N., Furumoto, S., Fodero‐Tavoletti, M. T., Mulligan, R. S., Harada, R., Yates, P. A., Pejoska, S., Kudo, Y., Masters, C. L., Yanai, K., et al. (2014) · Brain · doi:10.1093/brain/awu064 · Cited by 266 · see citing works
Models of β-amyloid induced Tau-pathology: The long and “folded” road to understand the mechanism
Stancu, I.-C., Vasconcelos, B., Terwel, D., & Dewachter, I. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-51 · Cited by 256 · see citing works
A role for tau at the synapse in Alzheimer’s disease pathogenesis
Pooler, A. M., Noble, W., & Hanger, D. P. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.09.018 · Cited by 203 · see citing works
Vasconcelos, B., Stancu, I.-C., Buist, A., Bird, M., Wang, P., Vanoosthuyse, A., Van Kolen, K., Verheyen, A., Kienlen-Campard, P., Octave, J.-N., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1525-x · Cited by 192 · see citing works
Sander, K., Lashley, T., Gami, P., Gendron, T., Lythgoe, M. F., Rohrer, J. D., Schott, J. M., Revesz, T., Fox, N. C., & Årstad, E. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.01.003 · Cited by 187 · see citing works
Gordon, B. A., Friedrichsen, K., Brier, M., Blazey, T., Su, Y., Christensen, J., Aldea, P., McConathy, J., Holtzman, D. M., Cairns, N. J., et al. (2016) · Brain · doi:10.1093/brain/aww139 · Cited by 184 · see citing works
Tau: From research to clinical development
Holtzman, D. M., Carrillo, M. C., Hendrix, J. A., Bain, L. J., Catafau, A. M., Gault, L. M., Goedert, M., Mandelkow, E., Mandelkow, E., Miller, D. S., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.018 · Cited by 139 · see citing works
Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease
Prohovnik, I., Perl, D. P., Davis, K. L., Libow, L. S., Lesser, G. T., & Haroutunian, V. H. (2006) · Neurology · doi:10.1212/01.wnl.0000191298.68045.50 · Cited by 129 · see citing works
Jack, C. R., Therneau, T. M., Wiste, H. J., Weigand, S. D., Knopman, D. S., Lowe, V. J., Mielke, M. M., Vemuri, P., Roberts, R. O., Machulda, M. M., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00323-3 · Cited by 129 · see citing works
Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly
Chhatwal, J. P., Schultz, A. P., Marshall, G. A., Boot, B., Gomez-Isla, T., Dumurgier, J., LaPoint, M., Scherzer, C., Roe, A. D., Hyman, B. T., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003050 · Cited by 106 · see citing works
Lockhart, S. N., Baker, S. L., Okamura, N., Furukawa, K., Ishiki, A., Furumoto, S., Tashiro, M., Yanai, K., Arai, H., Kudo, Y., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158460 · Cited by 94 · see citing works
Shcherbinin, S., Schwarz, A. J., Joshi, A. D., Navitsky, M. A., Flitter, M. L., Shankle, W. R., Devous, M. D., & Mintun, M. A. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.170027 · Cited by 93 · see citing works
Self-citationA Semiautomated Method for Quantification of F 18 Florbetapir PET Images
Joshi, A. D., Pontecorvo, M. J., Lu, M., Skovronsky, D., Mintun, M. A., & Devous, M. D. (2015) · Journal of Nuclear Medicine · doi:10.2967/jnumed.114.153494 · Cited by 92 · see citing works
Self-citationIkonomovic, M. D., Abrahamson, E. E., Price, J. C., Mathis, C. A., & Klunk, W. E. (2016) · Annals of Neurology · doi:10.1002/ana.24706 · Cited by 81 · see citing works
Neuropathologic features associated with Alzheimer disease diagnosis
Middleton, L. E., Grinberg, L. T., Miller, B. L., Kawas, C. H., & Yaffe, K. S. (2011) · Neurology · doi:10.1212/wnl.0b013e318236f0cf · Cited by 67 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
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
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
“Patients may exhibit Aβ plaque pathology for more than a decade before any clinical diagnosis of AD,(29,30) while tau pathology usually occurs downstream from the deposition of Aβ plaques.(31) It is thought that deposited Aβ can act as a damage-associated molecular pattern (DAMP) and bind to receptors like toll-like r…”
BackgroundSynergy between amyloid-β and tau in Alzheimer’s disease
Busche, M. A., & Hyman, B. T. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0687-6 · Cited by 1,242 · see citing works
Lecanemab: Appropriate Use Recommendations
Cummings, J., Apostolova, L., Rabinovici, G. D., Atri, A., Aisen, P., Greenberg, S., Hendrix, S., Selkoe, D., Weiner, M., Petersen, R. C., et al. (2023) · The Journal of Prevention of Alzheimer's Disease · doi:10.14283/jpad.2023.30 · Cited by 961 · see citing works
Self-citationAdvancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) investigators, Thijssen, E. H., La Joie, R., Wolf, A., Strom, A., Wang, P., Iaccarino, L., Bourakova, V., Cobigo, Y., Heuer, H., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0762-2 · Cited by 761 · see citing works
Alzheimer's disease drug development pipeline: 2019
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.05.008 · Cited by 762 · see citing works
The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics
Karran, E., & De Strooper, B. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00391-w · Cited by 742 · see citing works
Alzheimer’s disease drug development pipeline: 2022
Cummings, J., Lee, G., Nahed, P., Kambar, M. E. Z. N., Zhong, K., Fonseca, J., & Taghva, K. (2022) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12295 · Cited by 665 · see citing works
Imaging the evolution and pathophysiology of Alzheimer disease
Jagust, W. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0067-3 · Cited by 604 · see citing works
Ossenkoppele, R., Pichet Binette, A., Groot, C., Smith, R., Strandberg, O., Palmqvist, S., Stomrud, E., Tideman, P., Ohlsson, T., Jögi, J., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-02049-x · Cited by 496 · see citing works
Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
Busche, M. A., Wegmann, S., Dujardin, S., Commins, C., Schiantarelli, J., Klickstein, N., Kamath, T. V., Carlson, G. A., Nelken, I., & Hyman, B. T. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0289-8 · Cited by 413 · see citing works
Longitudinal 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
Fleisher, A. S., Pontecorvo, M. J., Devous, M. D., Lu, M., Arora, A. K., Truocchio, S. P., Aldea, P., Flitter, M., Locascio, T., Devine, M., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.0528 · Cited by 448 · see citing works
Self-citationTau and neuroinflammation: what impact for Alzheimer's disease and tauopathies?
Laurent, C., Buée, L., & Blum, D. (2018) · Biomedical Journal · doi:10.1016/j.bj.2018.01.003 · Cited by 348 · see citing works
Jack, C. R., Wiste, H. J., Botha, H., Weigand, S. D., Therneau, T. M., Knopman, D. S., Graff-Radford, J., Jones, D. T., Ferman, T. J., Boeve, B. F., et al. (2019) · Brain · doi:10.1093/brain/awz268 · Cited by 200 · see citing works
Shcherbinin, S., Evans, C. D., Lu, M., Andersen, S. W., Pontecorvo, M. J., Willis, B. A., Gueorguieva, I., Hauck, P. M., Brooks, D. A., Mintun, M. A., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.2793 · Cited by 210 · see citing works
Self-citationMicroglial activation and tau burden predict cognitive decline in Alzheimer’s disease
Malpetti, M., Kievit, R. A., Passamonti, L., Jones, P. S., Tsvetanov, K. A., Rittman, T., Mak, E., Nicastro, N., Bevan-Jones, W. R., Su, L., et al. (2020) · Brain · doi:10.1093/brain/awaa088 · Cited by 194 · see citing works
SPECT and PET imaging in Alzheimer’s disease
Valotassiou, V., Malamitsi, J., Papatriantafyllou, J., Dardiotis, E., Tsougos, I., Psimadas, D., Alexiou, S., Hadjigeorgiou, G., & Georgoulias, P. (2018) · Annals of Nuclear Medicine · doi:10.1007/s12149-018-1292-6 · Cited by 169 · see citing works
Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease
Iaccarino, L., Tammewar, G., Ayakta, N., Baker, S. L., Bejanin, A., Boxer, A. L., Gorno-Tempini, M. L., Janabi, M., Kramer, J. H., Lazaris, A., et al. (2018) · NeuroImage: Clinical · doi:10.1016/j.nicl.2017.09.016 · Cited by 165 · see citing works
Biomarker-Based Prediction of Longitudinal Tau Positron Emission Tomography in Alzheimer Disease
Leuzy, A., Smith, R., Cullen, N. C., Strandberg, O., Vogel, J. W., Binette, A. P., Borroni, E., Janelidze, S., Ohlsson, T., Jögi, J., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2021.4654 · Cited by 149 · see citing works
Cummings, J. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.05.006 · Cited by 140 · see citing works
Developing Effective Alzheimer’s Disease Therapies: Clinical Experience and Future Directions
Elmaleh, D. R., Farlow, M. R., Conti, P. S., Tompkins, R. G., Kundakovic, L., & Tanzi, R. E. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-190507 · Cited by 129 · see citing works
Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case.
Marquié, M., Verwer, E. E., Meltzer, A. C., Kim, S. J. W., Agüero, C., Gonzalez, J., Makaretz, S. J., Siao Tick Chong, M., Ramanan, P., Amaral, A. C., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0482-0 · Cited by 128 · see citing works
Predicting future rates of tau accumulation on PET
Jack, C. R., Wiste, H. J., Weigand, S. D., Therneau, T. M., Lowe, V. J., Knopman, D. S., Botha, H., Graff-Radford, J., Jones, D. T., Ferman, T. J., et al. (2020) · Brain · doi:10.1093/brain/awaa248 · Cited by 117 · see citing works
Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer’s disease
Sprugnoli, G., Munsch, F., Cappon, D., Paciorek, R., Macone, J., Connor, A., El Fakhri, G., Salvador, R., Ruffini, G., Donohoe, K., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00922-4 · Cited by 99 · see citing works
Flortaucipir F 18 quantitation using parametric estimation of reference signal intensity.
Southekal, S., Devous, M. D., Kennedy, I., Navitsky, M., Lu, M., Joshi, A. D., Pontecorvo, M. J., & Mintun, M. A. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.200006 · Cited by 92 · see citing works
Self-citationGobbi, L. C., Knust, H., Körner, M., Honer, M., Czech, C., Belli, S., Muri, D., Edelmann, M. R., Hartung, T., Erbsmehl, I., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00632 · Cited by 89 · see citing works
Test-retest reproducibility for the tau PET imaging agent flortaucipir F 18.
Devous, M. D., Joshi, A. D., Navitsky, M., Southekal, S., Pontecorvo, M. J., Shen, H., Lu, M., Shankle, W. R., Seibyl, J. P., Marek, K., et al. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.200691 · Cited by 79 · see citing works
Self-citationKnopman, D. S., Lundt, E. S., Therneau, T. M., Albertson, S. M., Gunter, J. L., Senjem, M. L., Schwarz, C. G., Mielke, M. M., Machulda, M. M., Boeve, B. F., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2020.3921 · Cited by 61 · see citing works
Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study
Parbo, P., Ismail, R., Sommerauer, M., Stokholm, M. G., Hansen, A. K., Hansen, K. V., Amidi, A., Schaldemose, J. L., Gottrup, H., Brændgaard, H., et al. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.06.004 · Cited by 63 · see citing works
In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer’s disease
Terada, T., Yokokura, M., Obi, T., Bunai, T., Yoshikawa, E., Ando, I., Shimada, H., Suhara, T., Higuchi, M., & Ouchi, Y. (2019) · Journal of Neurology · doi:10.1007/s00415-019-09400-2 · Cited by 60 · see citing works
Calpain-mediated tau fragmentation is altered in Alzheimer’s disease progression
Chen, H.-H., Liu, P., Auger, P., Lee, S.-H., Adolfsson, O., Rey-Bellet, L., Lafrance-Vanasse, J., Friedman, B. A., Pihlgren, M., Muhs, A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-35130-y · Cited by 51 · see citing works
MAO-B Inhibitors Do Not Block In Vivo Flortaucipir([18F]-AV-1451) Binding
Hansen, A. K., Brooks, D. J., & Borghammer, P. (2018) · Molecular Imaging and Biology · doi:10.1007/s11307-017-1143-1 · Cited by 51 · see citing works
Diagnostic biomarkers in Alzheimer’s disease
Andersen, E., Casteigne, B., Chapman, W. D., Creed, A., Foster, F., Lapins, A., Shatz, R., & Sawyer, R. P. (2021) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2021.100041 · Cited by 42 · see citing works
Albrecht, D. S., Sagare, A., Pachicano, M., Sweeney, M. D., Toga, A., Zlokovic, B., Chui, H., Joe, E., Schneider, L., Morris, J. C., et al. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.01.010 · Cited by 37 · see citing works
Gong, P., Chen, Y.-Q., Lin, A.-H., Zhang, H.-B., Zhang, Y., Ye, R. D., & Yu, Y. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00714-2 · Cited by 29 · see citing works
Zhang, H., Wang, D., Gong, P., Lin, A., Zhang, Y., Ye, R. D., & Yu, Y. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-180823 · Cited by 26 · see citing works
The Effects of Amyloid and Tau on Functional Network Connectivity in Older Populations
Wales, R. M., & Leung, H.-C. (2021) · Brain Connectivity · doi:10.1089/brain.2020.0902 · Cited by 26 · see citing works
Mulero-Franco, J., Jimenez-Herrera, R., Contreras, A., Djebari, S., Jiménez-Díaz, L., & Navarro-López, J. D. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118247 · Cited by 4 · see citing works
- Authors
- Pontecorvo, M. J., Devous, M. D., Navitsky, M., Lu, M., Salloway, S., Schaerf, F. W., Jennings, D., Arora, A. K., McGeehan, A., Lim, N. C., Xiong, H., Joshi, A. D., Siderowf, A., Mintun, M. A., & for the 18F-AV-1451-A05 investigators
- Affiliations
- Avid Radiopharmaceuticals (United States) (US)
- Butler Hospital (US)
- Corresponding author
- Pontecorvo, Michael J.
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-01-11
- Volume
- 140
- Issue
- 3
- Pages
- aww334
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC5382945
- OpenAlex
- W2573597225
- Cited by
- 357
- References
- 58
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 32 · 2023: 37 · 2022: 38 · 2021: 56 · 2020: 52 · 2019: 46 · 2018: 40 · 2017: 19
- FWCI
- 35.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Brain (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Avid Radiopharmaceuticals
- 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
- flortaucipir, tau PET, amyloid PET, florbetapir, Alzheimer's disease, mild cognitive impairment, amyloid-beta, tau protein, standard uptake value ratio, medial temporal lobe, hippocampus, amygdala, age, cognitive impairment, diagnosis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Analysis of Variance, Aniline Compounds, Brain, Cross-Sectional Studies, Ethylene Glycols, Female, Humans, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Amyloid beta-Peptides, tau Proteins, Radiopharmaceuticals, Positron-Emission Tomography, Young Adult, Cognitive Dysfunction
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
