Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum
Open accessPublished version of a preprint
Abstract
Tau phosphorylated at threonine 181 (p-tau181) measured in blood plasma has recently been proposed as an accessible, scalable, and highly specific biomarker for Alzheimer’s disease. Longitudinal studies, however, investigating the temporal dynamics of this novel biomarker are lacking. It is therefore unclear when in the disease process plasma p-tau181 increases above physiological levels and how it relates to the spatiotemporal progression of Alzheimer’s disease characteristic pathologies. We aimed to establish the natural time course of plasma p-tau181 across the sporadic Alzheimer’s disease spectrum in comparison to those of established imaging and fluid-derived biomarkers of Alzheimer’s disease. We examined longitudinal data from a large prospective cohort of elderly individuals enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n = 1067) covering a wide clinical spectrum from normal cognition to dementia, and with measures of plasma p-tau181 and an 18F-florbetapir amyloid-β PET scan at baseline. A subset of participants (n = 864) also had measures of amyloid-β1–42 and p-tau181 levels in CSF, and another subset (n = 298) had undergone an 18F-flortaucipir tau PET scan 6 years later. We performed brain-wide analyses to investigate the associations of plasma p-tau181 baseline levels and longitudinal change with progression of regional amyloid-β pathology and tau burden 6 years later, and estimated the time course of changes in plasma p-tau181 and other Alzheimer’s disease biomarkers using a previously developed method for the construction of long-term biomarker temporal trajectories using shorter-term longitudinal data. Smoothing splines demonstrated that earliest plasma p-tau181 changes occurred even before amyloid-β markers reached abnormal levels, with greater rates of change correlating with increased amyloid-β pathology. Voxel-wise PET analyses yielded relatively weak, yet significant, associations of plasma p-tau181 with amyloid-β pathology in early accumulating brain regions in cognitively healthy individuals, while the strongest associations with amyloid-β were observed in late accumulating regions in patients with mild cognitive impairment. Cross-sectional and particularly longitudinal measures of plasma p-tau181 were associated with widespread cortical tau aggregation 6 years later, covering temporoparietal regions typical for neurofibrillary tangle distribution in Alzheimer’s disease. Finally, we estimated that plasma p-tau181 reaches abnormal levels ∼6.5 and 5.7 years after CSF and PET measures of amyloid-β, respectively, following similar dynamics as CSF p-tau181. Our findings suggest that plasma p-tau181 increases are associated with the presence of widespread cortical amyloid-β pathology and with prospective Alzheimer’s disease typical tau aggregation, providing clear implications for the use of this novel blood biomarker as a diagnostic and screening tool for Alzheimer’s disease.
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?
Plasma p-tau-181 and plasma p-tau 217 may be useful in trials to assess impact on tau pathology of trial participants.
“Plasma p‐tau‐181 and plasma p‐tau 217 are elevated as AD advances and may be useful in trials to assess impact on tau pathology of trial participants. 28 , 29”
From Alzheimer’s disease drug development pipeline: 2021 (2021) · cites this paper as [28]
Plasma p-tau-181 and plasma p-tau 217 are elevated as AD advances.
“Plasma p‐tau‐181 and plasma p‐tau 217 are elevated as AD advances and may be useful in trials to assess impact on tau pathology of trial participants. 28 , 29”
From Alzheimer’s disease drug development pipeline: 2021 (2021) · cites this paper as [28]
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
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
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Dubois, B., Feldman, H. H., Jacova, C., Hampel, H., Molinuevo, J. L., Blennow, K., DeKosky, S. T., Gauthier, S., Selkoe, D., Bateman, R., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70090-0 · Cited by 3,321 · see citing works
Self-citationBraak, 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
Alzheimer's Disease Neuroimaging Initiative (ADNI)
Petersen, R. C., Aisen, P. S., Beckett, L. A., Donohue, M. C., Gamst, A. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Shaw, L. M., Toga, A. W., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181cb3e25 · Cited by 2,572 · cited 1× · see citing works
“ADNI inclusion criteria for the diagnostic cohorts have been described in detail elsewhere (Petersen et al. , 2010).”
Villemagne, V. L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K. A., Salvado, O., Szoeke, C., Macaulay, S. L., Martins, R., Maruff, P., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70044-9 · Cited by 2,279 · see citing works
High performance plasma amyloid-β biomarkers for Alzheimer's disease
Nakamura, A., Kaneko, N., Villemagne, V. L., Kato, T., Doecke, J., Doré, V., Fowler, C., Li, Q.-X., Martins, R., Rowe, C., et al. (2018) · Nature · doi:10.1038/nature25456 · Cited by 1,681 · see citing works
Palmqvist, S., Janelidze, S., Quiroz, Y. T., Zetterberg, H., Lopera, F., Stomrud, E., Su, Y., Chen, Y., Serrano, G. E., Leuzy, A., et al. (2020) · JAMA · doi:10.1001/jama.2020.12134 · Cited by 1,603 · see citing works
Self-citationThe Centiloid Project: standardizing quantitative amyloid plaque estimation by PET
Klunk, W. E., Koeppe, R. A., Price, J. C., Benzinger, T. L., Devous, M. D., Jagust, W. J., Johnson, K. A., Mathis, C. A., Minhas, D., Pontecorvo, M. J., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.07.003 · Cited by 1,348 · see citing works
Karikari, T. K., Pascoal, T. A., Ashton, N. J., Janelidze, S., Benedet, A. L., Rodriguez, J. L., Chamoun, M., Savard, M., Kang, M. S., Therriault, J., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30071-5 · Cited by 1,316 · see citing works
Self-citationJanelidze, S., Mattsson, N., Palmqvist, S., Smith, R., Beach, T. G., Serrano, G. E., Chai, X., Proctor, N. K., Eichenlaub, U., Zetterberg, H., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0755-1 · Cited by 1,247 · see citing works
Self-citationPET 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
Self-citationTau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · cited 1× · see citing works
“Nevertheless, the fact that plasma p-tau181 correlated with the severity of tau pathology several years later suggests that this marker may be particularly useful for screening participants in clinical trials targeting tau pathology (Congdon and Sigurdsson, 2018).”
Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease
Mattsson, N., Andreasson, U., Zetterberg, H., Blennow, K., & Initiative, F. T. A. D. N. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2016.6117 · Cited by 1,070 · see citing works
Self-citationTau 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
Defining imaging biomarker cut points for brain aging and Alzheimer's disease
Jack, C. R., Wiste, H. J., Weigand, S. D., Therneau, T. M., Lowe, V. J., Knopman, D. S., Gunter, J. L., Senjem, M. L., Jones, D. T., Kantarci, K., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.08.005 · Cited by 931 · see citing works
Palmqvist, S., Schöll, M., Strandberg, O., Mattsson, N., Stomrud, E., Zetterberg, H., Blennow, K., Landau, S., Jagust, W., & Hansson, O. (2017) · Nature Communications · doi:10.1038/s41467-017-01150-x · Cited by 911 · see citing works
Self-citationHigh-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis
Schindler, S. E., Bollinger, J. G., Ovod, V., Mawuenyega, K. G., Li, Y., Gordon, B. A., Holtzman, D. M., Morris, J. C., Benzinger, T. L. S., Xiong, C., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000008081 · Cited by 885 · see citing works
Jin, M., Shepardson, N., Yang, T., Chen, G., Walsh, D., & Selkoe, D. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017033108 · Cited by 876 · 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
Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease
Villemagne, V. L., Pike, K. E., Chételat, G., Ellis, K. A., Mulligan, R. S., Bourgeat, P., Ackermann, U., Jones, G., Szoeke, C., Salvado, O., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22248 · Cited by 833 · see citing works
Hansson, O., Seibyl, J., Stomrud, E., Zetterberg, H., Trojanowski, J. Q., Bittner, T., Lifke, V., Corradini, V., Eichenlaub, U., Batrla, R., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.01.010 · Cited by 808 · see citing works
Self-citationTau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease
Bejanin, A., Schonhaut, D. R., La Joie, R., Kramer, J. H., Baker, S. L., Sosa, N., Ayakta, N., Cantwell, A., Janabi, M., Lauriola, M., et al. (2017) · Brain · doi:10.1093/brain/awx243 · Cited by 778 · see citing works
Advancing 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
Self-citationThe A4 Study: Stopping AD Before Symptoms Begin?
Sperling, R. A., Rentz, D. M., Johnson, K. A., Karlawish, J. H., Donohue, M., Salmon, D. P., & Aisen, P. S. S. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007941 · Cited by 756 · 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
Mattsson, N., Cullen, N. C., Andreasson, U., Zetterberg, H., & Blennow, K. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.0765 · Cited by 726 · see citing works
Self-citationRabinovici, G. D., Gatsonis, C., Apgar, C., Chaudhary, K., Gareen, I., Hanna, L., Hendrix, J., Hillner, B. E., Olson, C., Lesman-Segev, O. H., et al. (2019) · JAMA · doi:10.1001/jama.2019.2000 · Cited by 674 · see citing works
Mielke, M. M., Hagen, C. E., Xu, J., Chai, X., Vemuri, P., Lowe, V. J., Airey, D. C., Knopman, D. S., Roberts, R. O., Machulda, M. M., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.013 · Cited by 621 · see citing works
Ovod, V., Ramsey, K. N., Mawuenyega, K. G., Bollinger, J. G., Hicks, T., Schneider, T., Sullivan, M., Paumier, K., Holtzman, D. M., Morris, J. C., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.06.2266 · Cited by 585 · see citing works
Plasma tau in Alzheimer disease
Mattsson, N., Zetterberg, H., Janelidze, S., Insel, P. S., Andreasson, U., Stomrud, E., Palmqvist, S., Baker, D., Tan Hehir, C. A., Jeromin, A., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003246 · Cited by 502 · see citing works
Self-citationOssenkoppele, R., Rabinovici, G. D., Smith, R., Cho, H., Schöll, M., Strandberg, O., Palmqvist, S., Mattsson, N., Janelidze, S., Santillo, A., et al. (2018) · JAMA · doi:10.1001/jama.2018.12917 · Cited by 472 · see citing works
Self-citationAmyloid biomarkers in Alzheimer's disease
Blennow, K., Mattsson, N., Schöll, M., Hansson, O., & Zetterberg, H. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.03.002 · Cited by 470 · see citing works
Self-citationLandau, S. M., Breault, C., Joshi, A. D., Pontecorvo, M. J., Mathis, C. A., Jagust, W. J., & Mintun, M. A. (2012) · Journal of Nuclear Medicine · doi:10.2967/jnumed.112.109009 · Cited by 465 · see citing works
Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease
Maass, A., Landau, S., Baker, S. L., Horng, A., Lockhart, S. N., La Joie, R., Rabinovici, G. D., & Jagust, W. J. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.05.058 · Cited by 462 · see citing works
In vivo staging of regional amyloid deposition
Grothe, M. J., Barthel, H., Sepulcre, J., Dyrba, M., Sabri, O., Teipel, S. J., Initiative, F. T. A. D. N., Initiative, A. D. N., Weiner, M., Aisen, P., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004643 · Cited by 440 · see citing works
Self-citationBlood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease
Barthélemy, N. R., Horie, K., Sato, C., & Bateman, R. J. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20200861 · Cited by 437 · see citing works
Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers
De Felice, F. G., Wu, D., Lambert, M. P., Fernandez, S. J., Velasco, P. T., Lacor, P. N., Bigio, E. H., Jerecic, J., Acton, P. J., Shughrue, P. J., et al. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.02.029 · Cited by 432 · see citing works
Brain β-amyloid load approaches a plateau
Jack, C. R., Wiste, H. J., Lesnick, T. G., Weigand, S. D., Knopman, D. S., Vemuri, P., Pankratz, V. S., Senjem, M. L., Gunter, J. L., Mielke, M. M., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182840bbe · Cited by 406 · see citing works
Bittner, T., Zetterberg, H., Teunissen, C. E., Ostlund, R. E., Militello, M., Andreasson, U., Hubeek, I., Gibson, D., Chu, D. C., Eichenlaub, U., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.09.009 · Cited by 374 · see citing works
Mattsson-Carlgren, N., Andersson, E., Janelidze, S., Ossenkoppele, R., Insel, P., Strandberg, O., Zetterberg, H., Rosen, H. J., Rabinovici, G., Chai, X., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz2387 · Cited by 359 · cited 1× · see citing works
“This is in line with previous in vitro (De Felice et al. , 2008; Jin et al. , 2011) and in vivo animal findings (Zheng et al. , 2002; Shin et al. , 2007), as well as results from recent reports on p-tau181 in CSF (Palmqvist et al. , 2019; Mattsson-Carlgren et al. , 2020).”
Self-citationPalmqvist, S., Insel, P. S., Stomrud, E., Janelidze, S., Zetterberg, H., Brix, B., Eichenlaub, U., Dage, J. L., Chai, X., Blennow, K., et al. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201911170 · Cited by 353 · see citing works
Self-citationLantero Rodriguez, J., Karikari, T. K., Suárez-Calvet, M., Troakes, C., King, A., Emersic, A., Aarsland, D., Hye, A., Zetterberg, H., Blennow, K., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02195-x · Cited by 350 · see citing works
Self-citationZheng, W.-H., Bastianetto, S., Mennicken, F., Ma, W., & Kar, S. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00404-9 · Cited by 321 · see citing works
Thomas, B. A., Erlandsson, K., Marc Modat, A., Thurfjell, L., Vandenberghe, R. R., Sebastien Ourselin, A., & Hutton, B. F. (2011) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-011-1745-9 · Cited by 317 · see citing works
La Joie, R., Ayakta, N., Seeley, W. W., Borys, E., Boxer, A. L., DeCarli, C., Doré, V., Grinberg, L. T., Huang, E., Hwang, J., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.09.001 · Cited by 317 · see citing works
Considerations and code for partial volume correcting [ 18 F]-AV-1451 tau PET data
Baker, S. L., Maaß, A., & Jagust, W. J. (2017) · Data in Brief · doi:10.1016/j.dib.2017.10.024 · Cited by 298 · see citing works
The Alzheimer's Disease Neuroimaging Initiative 2 PET Core: 2015
Jagust, W. J., Landau, S. M., Koeppe, R. A., Reiman, E. M., Chen, K., Mathis, C. A., Price, J. C., Foster, N. L., & Wang, A. Y. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.05.001 · Cited by 294 · see citing works
In vivo staging of regional amyloid deposition
Grothe, M. J., Barthel, H., Sepulcre, J., Dyrba, M., Sabri, O., Teipel, S. J., Stern, Y., & Initiative, A. D. N. (2022) · DZNE Pub · doi:10.7916/0vj1-4c02 · Cited by 294 · see citing works
Self-citationCerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging
Schindler, S. E., Gray, J. D., Gordon, B. A., Xiong, C., Batrla‐Utermann, R., Quan, M., Wahl, S., Benzinger, T. L. S., Holtzman, D. M., Morris, J. C., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.01.013 · Cited by 284 · see citing works
White matter hyperintensities: relationship to amyloid and tau burden
Graff-Radford, J., Arenaza-Urquijo, E. M., Knopman, D. S., Schwarz, C. G., Brown, R. D., Rabinstein, A. A., Gunter, J. L., Senjem, M. L., Przybelski, S. A., Lesnick, T., et al. (2019) · Brain · doi:10.1093/brain/awz162 · Cited by 253 · 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
Self-citationMagnetic resonance imaging in Alzheimer’s disease neuroimaging initiative 2
Jack, C. R., Barnes, J., Bernstein, M. A., Borowski, B. J., Brewer, J., Clegg, S., Dale, A. M., Carmichael, O., Ching, C., DeCarli, C., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.05.002 · Cited by 220 · see citing works
Mielke, M. M., Hagen, C. E., Wennberg, A. M. V., Airey, D. C., Savica, R., Knopman, D. S., Machulda, M. M., Roberts, R. O., Jack, C. R., Petersen, R. C., et al. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.1359 · Cited by 209 · see citing works
High performance plasma amyloid-beta biomarkers for Alzheimer's disease
Nakamura, A., Kaneko, N., Villemagne, V. L., Kato, T., Doecke, J. D., Doré, V., Fowler, C. J., Li, Q., Martins, R. N., Rowe, C. C., et al. (2018) · Nature · Cited by 196 · see citing works
Blennow, K., Shaw, L. M. J., Stomrud, E., Mattsson, N., Toledo, J. B., Buck, K., Wahl, S., Eichenlaub, U., Lifke, V., Simon, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-54204-z · Cited by 193 · see citing works
Self-citationGonzález‐Escamilla, G., Lange, C., Teipel, S. J., Buchert, R., & Grothe, M. J. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.12.077 · Cited by 186 · see citing works
Self-citationAn update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders
Ashton, N. J., Hye, A., Rajkumar, A. P., Leuzy, A., Snowden, S. G., Suárez‐Calvet, M., Karikari, T. K., Schöll, M., Joie, R. L., Rabinovici, G. D., et al. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0348-0 · Cited by 182 · see citing works
Self-citationVergallo, A., Mégret, L., Lista, S., Cavedo, E., Zetterberg, H., Blennow, K., Vanmechelen, E., Vos, A. D., Habert, M., Potier, M., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.03.009 · Cited by 173 · see citing works
Self-citationDiagnostic and prognostic value of serum NfL and p-Tau 181 in frontotemporal lobar degeneration
Benussi, A., Karikari, T. K., Ashton, N. J., Gazzina, S., Premi, E., Benussi, L., Ghidoni, R., Lantero‐Rodriguez, J., Emeršič, A., Simrén, J., et al. (2020) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-323487 · Cited by 156 · see citing works
Self-citationPET staging of amyloidosis using striatum
Hanseeuw, B. J., Betensky, R. A., Mormino, E. C., Schultz, A. P., Sepulcre, J., Becker, J. A., Jacobs, H. I. L., Buckley, R. F., LaPoint, M. R., Vannini, P., et al. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.04.011 · Cited by 134 · see citing works
Blood-based biomarkers for Alzheimer’s disease—An update
Zetterberg, H. (2018) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2018.10.025 · Cited by 128 · see citing works
Self-citationMeyer, P., Binette, A. P., Gonneaud, J., Breitner, J. C. S., Villeneuve, S., & ADNI Investigators (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4749 · Cited by 123 · see citing works
O’Connor, A., Karikari, T. K., Poole, T., Ashton, N. J., Lantero Rodriguez, J., Khatun, A., Swift, I., Heslegrave, A. J., Abel, E., Chung, E., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0838-x · Cited by 122 · see citing works
Self-citationWillemse, E. A. J., van Maurik, I. S., Tijms, B. M., Bouwman, F. H., Franke, A., Hubeek, I., Boelaarts, L., Claus, J. J., Korf, E. S. C., van Marum, R. J., et al. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.08.006 · Cited by 104 · see citing works
The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans
Kang, J., Korecka, M., Figurski, M., Toledo, J. B., Blennow, K., Zetterberg, H., Waligórska, T., Brylska, M., Fields, L., Shah, N., et al. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.05.003 · Cited by 98 · see citing works
Self-citationPlasma amyloid beta levels are associated with cerebral amyloid and tau deposition
Risacher, S. L., Fandos, N., Romero, J., Sherriff, I., Pesini, P., Saykin, A. J., & Apostolova, L. G. (2019) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2019.05.007 · Cited by 96 · see citing works
A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer’s disease
Ashton, N. J., Nevado‐Holgado, A. J., Barber, I., Lynham, S., Gupta, V. B., Chatterjee, P., Goozee, K. G., Hone, E., Pedrini, S., Blennow, K., et al. (2019) · Science Advances · doi:10.1126/sciadv.aau7220 · Cited by 83 · see citing works
Self-citationDerivation of cutoffs for the Elecsys® amyloid β (1–42) assay in Alzheimer's disease
Shaw, L. M. J., Waligórska, T., Fields, L., Korecka, M., Figurski, M., Trojanowski, J. Q., Eichenlaub, U., Wahl, S., Quan, M., Pontecorvo, M. J., et al. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.07.002 · Cited by 81 · see citing works
Shin, R., Ogino, K., Shimabuku, A., Taki, T., Nakashima, H., Ishihara, T., & Kitamoto, T. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0211-z · Cited by 57 · see citing works
Caballero, M. Á. A., Song, Z., Rubinski, A., Duering, M., Dichgans, M., Park, D. C., & Ewers, M. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12062 · Cited by 51 · see citing works
White matter hyperintensities are associated with subthreshold amyloid accumulation
Moscoso, A., Rey-Bretal, D., Silva-Rodríguez, J., Aldrey, J. M., Cortés, J., Pías-Peleteiro, J., Ruibal, Á., & Aguiar, P. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116944 · Cited by 49 · cited 1× · see citing works
“Our findings can thus not easily be extrapolated to the population at large, and possible effects of vascular pathology (Graff-Radford et al., 2019; Caballero et al., 2020; Moscoso et al., 2020) and other common comorbidities on amyloid-b and plasma p-tau181 levels remain to be studied in less selected cohorts.”
Temporal trajectories of in vivo tau and amyloid-β accumulation in Alzheimer’s disease
Baek, M. S., Cho, H., Lee, H. S., Choi, J. Y., Lee, J., Ryu, Y. H., Lee, M. S., & Lyoo, C. H. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-04773-3 · Cited by 36 · see citing works
Budgeon, C. A., Murray, K., Turlach, B. A., Baker, S. A., Villemagne, V. L., Burnham, S. C., & Initiative, A. D. N. (2017) · Statistics in Medicine · doi:10.1002/sim.7300 · Cited by 33 · see citing works
The transformative potential of plasma phosphorylated tau
Jack, C. R. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30112-5 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology.
Ashton, N. J., Pascoal, T. A., Karikari, T. K., Benedet, A. L., Lantero-Rodriguez, J., Brinkmalm, G., Snellman, A., Schöll, M., Troakes, C., Hye, A., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02275-6 · Cited by 719 · see citing works
Self-citationTau biomarkers in Alzheimer's disease: towards implementation in clinical practice and trials
Ossenkoppele, R., van der Kant, R., & Hansson, O. (2022) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00168-5 · Cited by 557 · see citing works
Alzheimer’s disease drug development pipeline: 2021
Cummings, J., Lee, G., Zhong, K., Fonseca, J., & Taghva, K. (2021) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12179 · Cited by 539 · see citing works
Blood biomarkers for Alzheimer’s disease in clinical practice and trials
Hansson, O., Blennow, K., Zetterberg, H., & Dage, J. (2023) · Nature Aging · doi:10.1038/s43587-023-00403-3 · Cited by 522 · see citing works
Self-citationPerformance of plasma phosphorylated tau 181 and 217 in the community
Mielke, M. M., Dage, J. L., Frank, R. D., Algeciras-Schimnich, A., Knopman, D. S., Lowe, V. J., Bu, G., Vemuri, P., Graff-Radford, J., Jack, C. R., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01822-2 · Cited by 465 · see citing works
Hampel, H., Hu, Y., Cummings, J., Mattke, S., Iwatsubo, T., Nakamura, A., Vellas, B., O’Bryant, S., Shaw, L. M., Cho, M., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.05.017 · Cited by 283 · see citing works
Self-citationCSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease
Horie, K., Salvadó, G., Barthélemy, N. R., Janelidze, S., Li, Y., He, Y., Saef, B., Chen, C. D., Jiang, H., Strandberg, O., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02443-z · Cited by 249 · see citing works
Mielke, M. M., Frank, R. D., Dage, J. L., Jeromin, A., Ashton, N. J., Blennow, K., Karikari, T. K., Vanmechelen, E., Zetterberg, H., Algeciras-Schimnich, A., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.2293 · Cited by 244 · see citing works
Self-citationDiagnostic and prognostic plasma biomarkers for preclinical Alzheimer’s disease
Chatterjee, P., Pedrini, S., Ashton, N. J., Tegg, M., Goozee, K., Singh, A. K., Karikari, T. K., Simrén, J., Vanmechelen, E., Armstrong, N. J., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12447 · Cited by 231 · see citing works
Self-citationDesigning the next-generation clinical care pathway for Alzheimer’s disease
Hampel, H., Au, R., Mattke, S., van der Flier, W. M., Aisen, P., Apostolova, L., Chen, C., Cho, M., De Santi, S., Gao, P., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00269-x · Cited by 191 · see citing works
Veitch, D. P., Weiner, M. W., Aisen, P. S., Beckett, L. A., DeCarli, C., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Landau, S. M., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12422 · Cited by 184 · see citing works
Diagnostic value of serum versus plasma phospho-tau for Alzheimer’s disease
Kac, P. R., Gonzalez-Ortiz, F., Simrén, J., Dewit, N., Vanmechelen, E., Zetterberg, H., Blennow, K., Ashton, N. J., & Karikari, T. K. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01011-w · Cited by 73 · see citing works
Self-citationAssociation of plasma P-tau181 with memory decline in non-demented adults
Therriault, J., Benedet, A. L., Pascoal, T. A., Lussier, F. Z., Tissot, C., Karikari, T. K., Ashton, N. J., Chamoun, M., Bezgin, G., Mathotaarachchi, S., et al. (2021) · Brain Communications · doi:10.1093/braincomms/fcab136 · Cited by 56 · see citing works
Self-citation
- Authors
- Moscoso, A., Grothe, M. J., Ashton, N. J., Karikari, T. K., Rodriguez, J. L., Snellman, A., Suárez-Calvet, M., Zetterberg, H., Blennow, K., Schöll, M., & Initiative, F. T. A. D. N.
- Affiliations
- Wallenberg Centre for Molecular and Translational Medicine (SE)
- Instituto de Biomedicina de Sevilla (ES)
- King's College London (GB)
- University of Gothenburg (SE)
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden
- University of Turku (FI)
- Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain
- Sahlgrenska University Hospital (SE)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Schöll, Michael
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-11-30
- Volume
- 144
- Issue
- 1
- Pages
- 325-339
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC7880671
- OpenAlex
- W3107511586
- Cited by
- 229
- References
- 75
- Citations by year
- 2026: 16 · 2025: 31 · 2024: 42 · 2023: 46 · 2022: 54 · 2021: 38 · 2020: 1
- FWCI
- 25.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain (publishedVersion, cc-by-nc)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by-nc)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by-nc)
- UTUPub (University of Turku) (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- “Miguel Servet” program (CP19/00031)
- Spanish Instituto de Salud Carlos III
- Brightfocus Foundation (#A2020812F)
- Swedish Alzheimer Foundation (#AF-930627, #AF-742881, #AF-740191)
- Swedish Brain Foundation (#FO2020-0240)
- Swedish Dementia Foundation
- Agneta Prytz-Folkes & Gösta Folkes Foundation (#2020-00124)
- Wallströms and Mary-Ann Sjöbloms Foundation
- Anna Lisa and Brother Björnsson’s Foundation
- Gamla Tjänarinnor
- Gun and Bertil Stohnes Foundation
- Paulo Foundation
- Orion Research Foundation
- European Union’s Horizon 2020 Research and Innovation Program (752310)
- Instituto de Salud Carlos III (PI19/00155)
- Spanish Ministry of Science, Innovation and Universities (IJC2018-037478-I)
- Swedish Research Council (#2018-02532, #2017-00915, #2017-02869)
- European Research Council (#681712)
- Swedish State Support for Clinical Research (#ALFGBG-720931)
- Alzheimer Drug Discovery Foundation (#201809-2016862, #RDAPB-201809-2016615)
- Hjärnfonden (#FO2017-0243)
- ALF-agreement (#ALFGBG-715986, #ALFGBG-813971)
- European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236)
- Knut and Alice Wallenberg Foundation (KAW 2014.0363)
- National Institutes of Health (U01 AG024904)
- Department of Defense award (W81XWH-12-2-0012)
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer’s Association
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- plasma biomarkers, Alzheimer's disease, amyloid-beta pathology, tau PET, neurofibrillary tangles, mild cognitive impairment, longitudinal biomarker dynamics, cerebrospinal fluid biomarkers, amyloid-beta 42, disease progression, ADNI cohort, smoothing splines
- MeSH terms
- Alzheimer Disease, Brain, Humans, Longitudinal Studies, Phosphorylation, Prospective Studies, Threonine, Biomarkers, tau Proteins, Disease Progression, Positron-Emission Tomography
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
