Tau Phosphorylation Rates Measured by Mass Spectrometry Differ in the Intracellular Brain vs. Extracellular Cerebrospinal Fluid Compartments and Are Differentially Affected by Alzheimer’s Disease

Barthélemy, Nicolas R.; Mallipeddi, Nipun; Moiseyev, Paul; Sato, Chihiro; Bateman, Randall J.

doi:10.3389/fnagi.2019.00121

Cited by 156Alzheimer's disease research and treatmentsAdvanced Proteomics Techniques and ApplicationsDementia and Cognitive Impairment Research

Tau Phosphorylation Rates Measured by Mass Spectrometry Differ in the Intracellular Brain vs. Extracellular Cerebrospinal Fluid Compartments and Are Differentially Affected by Alzheimer’s Disease

Open access

Barthélemy, Nicolas R., Mallipeddi, Nipun, Moiseyev, Paul, Sato, Chihiro, Bateman, Randall J.·2019·Frontiers in Aging Neuroscience

DOI 10.3389/fnagi.2019.00121PMC PMC6537657

Open this paper in CoChat — free account Open PDF

Abstract

Tau protein aggregation into neurofibrillary tangles in the central nervous system contributes to the etiology of certain neurodegenerative disorders, including Alzheimer's disease (AD). Though the mechanism of tau destabilization is not fully understood yet, tau protein has been found to be hyperphosphorylated in tau aggregates. To investigate this further, we developed a highly sensitive and specific mass spectrometry (MS) method using parallel reaction monitoring (PRM) to identify tau phosphorylation sites. This method enables us to compare the abundance of phosphorylation sites in tau proteins in the brain and cerebrospinal fluid (CSF) in humans with and without AD. We detected 29 distinct phosphorylated tau (p-tau) sites in full-length tau from soluble human brain lysate and 12 sites on truncated tau in CSF, mainly in the mid-domain. Brain soluble tau phosphorylation sites are localized on three domains including a proline-rich mid-domain, the C-terminus, and a cluster on the N-terminal projection domain not previously characterized. Some phosphorylation sites increased in CSF, while others decreased compared to brain. Notably, phosphorylation on T205 and S208, recognized by AT8 antibody defining Braak stages of brain tau aggregation, were not detected in normal brain soluble tau but were found in the CSF. Comparison of the p-tau rates from the brain and the CSF indicated that the abundance of phosphorylated sites varied in a site-specific manner. CSF tau proteins from non-AD participants were significantly hyperphosphorylated on T111, T205, S208, T217 and T231. In AD CSF, hyperphosphorylation on these sites was exacerbated, and phosphorylation on T153 and T175 specifically were detected. This supports the hypothesis that tau hyperphosphorylation could be a physiological process amplified by AD pathology. Conversely, we found that S202 was hypophosphorylated in CSF and was not hyperphosphorylated in AD, demonstrating that p-tau isoforms could have different metabolisms depending on which sites are phosphorylated. These site-specific p-tau rates are independent of tau concentration and distinct of current CSF tau and p-tau assays measuring tau isoforms levels. Targeted MS multiplexing ability and high-throughput capacity lets us envision the use of these new p-tau measurements as promising biomarkers for AD diagnosis and tracking therapeutic responses.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.3389/fnagi.2019.00121

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

A recent mass spectrometry-based study found increased degree of phosphorylation at position 217 compared with position 181 in CSF from patients with AD.
“a recent mass spectrometry–based study found increased degree of phosphorylation at position 217 compared with position 181 in CSF from patients with AD (9).”
From Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive tau PET in Alzheimer's disease (2020) · cites this paper as [9]

Self-check

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

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

Staging of alzheimer's disease-related neurofibrillary changes
Braak, H., & Braak, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00021-6 · Cited by 2,357 · see citing works
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251 · see citing works
Parallel reaction monitoring for high resolution and high mass accuracy quantitative, targeted proteomics
Peterson, A. C., Russell, J. D., Bailey, D. J., Westphall, M. S., & Coon, J. J. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o112.020131 · Cited by 1,288 · 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 pathology in Alzheimer disease and other tauopathies
Iqbal, K., del C. Alonso, A., Chen, S., Chohan, M. O., El-Akkad, E., Gong, C.-X., Khatoon, S., Li, B., Liu, F., Rahman, A., et al. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.09.008 · Cited by 1,037 · see citing works
Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease
Augustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T. (2002) · Acta Neuropathologica · doi:10.1007/s004010100423 · Cited by 998 · see citing works
Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments
Alonso, A. D. C., Zaidi, T., Novák, M., Grundke, I., & Iqbal, K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121119298 · Cited by 968 · see citing works
Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: Distinction between PHF-like immunoreactivity and microtubule binding
Biernat, J., Gustke, N., Drewes, G., Mandelkow, E., & Mandelkow, E. (1993) · Neuron · doi:10.1016/0896-6273(93)90279-z · Cited by 796 · see citing works
Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease.
Köpke, E., Tung, Y. C., Shaikh, S., Alonso, A. C., Iqbal, K., & Grundke-Iqbal, I. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80536-5 · Cited by 779 · see citing works
Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau.
Matsuo, E. S., Shin, R., Billingsley, M., de Voorde, A. V., O'Connor, M., Trojanowski, J., & Lee, V. (1994) · Neuron · doi:10.1016/0896-6273(94)90264-x · Cited by 588 · see citing works
Tau Kinetics in Neurons and the Human Central Nervous System
Sato, C., Barthélemy, N. R., Mawuenyega, K. G., Patterson, B. W., Gordon, B. A., Jockel-Balsarotti, J., Sullivan, M., Crisp, M. J., Kasten, T., Kirmess, K. M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.015 · Cited by 586 · see citing works
Self-citation
Neuronal activity regulates extracellular tau in vivo
Yamada, K., Holth, J. K., Liao, F., Stewart, F. R., Mahan, T. E., Jiang, H., Cirrito, J. R., Patel, T. K., Hochgräfe, K., Mandelkow, E., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131685 · Cited by 574 · see citing works
Targeted Proteomic Quantification on Quadrupole-Orbitrap Mass Spectrometer
Gallien, S., Duriez, E., Crone, C., Kellmann, M., Moehring, T., & Domon, B. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o112.019802 · Cited by 510 · see citing works
Tau imaging: early progress and future directions
Villemagne, V. L., Fodero-Tavoletti, M. T., Masters, C. L., & Rowe, C. C. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70252-2 · Cited by 501 · see citing works
Quantitative analysis of peptides and proteins in biomedicine by targeted mass spectrometry
Gillette, M. A., & Carr, S. A. (2012) · Nature Methods · doi:10.1038/nmeth.2309 · Cited by 497 · see citing works
Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice
Morris, M., Knudsen, G. M., Maeda, S., Trinidad, J. C., Ioanoviciu, A., Burlingame, A. L., & Mucke, L. (2015) · Nature Neuroscience · doi:10.1038/nn.4067 · Cited by 472 · see citing works
Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis
Hanger, D. P., Byers, H. L., Wray, S., Leung, K.-Y., Saxton, M. J., Seereeram, A., Reynolds, C. H., Ward, M. A., & Anderton, B. H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703269200 · Cited by 455 · see citing works
Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain
Hasegawa, M., Morishima-Kawashima, M., Takio, K., Suzuki, M., Titani, K., & Ihara, Y. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41890-x · Cited by 430 · see citing works
Phosphorylation of different tau sites during progression of Alzheimer’s disease
Neddens, J., Temmel, M., Flunkert, S., Kerschbaumer, B., Hoeller, C., Loeffler, T., Niederkofler, V., Daum, G., Attems, J., & Hutter-Paier, B. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0557-6 · Cited by 384 · see citing works
New Phosphorylation Sites Identified in Hyperphosphorylated Tau (Paired Helical Filament‐Tau) from Alzheimer's Disease Brain Using Nanoelectrospray Mass Spectrometry
Hanger, D. P., Betts, J. C., Loviny, T. L. F., Blackstock, W. P., & Anderton, B. H. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.71062465.x · Cited by 378 · see citing works
Decreased cerebrospinal fluid Aβ <sub>42</sub> correlates with brain atrophy in cognitively normal elderly
Fagan, A. M., Head, D., Shah, A. R., Marcus, D., Mintun, M., Morris, J. C., & Holtzman, D. M. (2009) · Annals of Neurology · doi:10.1002/ana.21559 · Cited by 327 · cited 1× · see citing works
“T111, T205, S208 and T217 were more hyperphosphorylated than T181, which is the most commonly measured target used as a p-tau biomarker for AD (Fagan et al., 2009).”
Background
Identification of the Tau phosphorylation pattern that drives its aggregation
Despres, C., Byrne, C., Qi, H., Cantrelle, F., Huvent, I., Chambraud, B., Baulieu, É.-É., Jacquot, Y., Landrieu, I., Lippens, G. M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1708448114 · Cited by 246 · see citing works
Technical considerations for large-scale parallel reaction monitoring analysis
Gallien, S., Bourmaud, A., Kim, S.-Y., & Domon, B. (2013) · Journal of Proteomics · doi:10.1016/j.jprot.2013.10.029 · Cited by 198 · see citing works
Extracellular Tau Levels Are Influenced by Variability in Tau That Is Associated with Tauopathies
Karch, C. M. M., Jeng, A. T., & Goate, A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.380642 · Cited by 171 · see citing works
C-Terminally Truncated Forms of Tau, But Not Full-Length Tau or Its C-Terminal Fragments, Are Released from Neurons Independently of Cell Death
Kanmert, D., Cantlon, A., Muratore, C., Jin, M., O’Malley, T. T., Lee, G. S., Young‐Pearse, T. L., Selkoe, D. J., & Walsh, D. M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0387-15.2015 · Cited by 159 · see citing works
FLEXITau: Quantifying Post-translational Modifications of Tau Protein in Vitro and in Human Disease
Mair, W., Muntel, J., Tepper, K., Tang, S., Biernat, J., Seeley, W. W., Kosik, K. S., Mandelkow�, E., Steen, H., & Steen, J. A. J. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.5b04509 · Cited by 144 · see citing works
Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity
Funk, K. E., Thomas, S. N., Schafer, K. N., Cooper, G. L., Liao, Z., Clark, D. J., Yang, A. J., & Kuret, J. (2014) · Biochemical Journal · doi:10.1042/bj20140372 · Cited by 142 · see citing works
Epitope mapping and structural basis for the recognition of phosphorylated tau by the anti‐tau antibody AT8
Malia, T., Teplyakov, A., Ernst, R., Wu, S., Lacy, E. R., Liu, X., Vandermeeren, M., Mercken, M. H., Luo, J., Sweet, R. W., et al. (2016) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24988 · Cited by 136 · see citing works
Dual modification of Alzheimer’s disease PHF-tau protein by lysine methylation and ubiquitylation: a mass spectrometry approach
Thomas, S. N., Funk, K. E., Wan, Y., Liao, Z., Davies, P., Kuret, J., & Yang, A. J. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0893-0 · Cited by 123 · see citing works
Tau Protein Quantification in Human Cerebrospinal Fluid by Targeted Mass Spectrometry at High Sequence Coverage Provides Insights into Its Primary Structure Heterogeneity
Barthélemy, N. R., Fenaille, F., Hirtz, C., Sergeant, N., Schraen-Maschke, S., Vialaret, J., Buée, L., Gabelle, A., Junot, C., Lehmann, S., et al. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b01001 · Cited by 123 · see citing works
Self-citation
Application of synthetic phospho‐ and unphospho‐ peptides to identify phosphorylation sites in a subregion of the tau molecule, which is modified in Alzheimer's disease
Liu, W.-K., Moore, W. T., Williams, R., Hall, F. L., & Yen, S. (1993) · Journal of Neuroscience Research · doi:10.1002/jnr.490340315 · Cited by 69 · see citing works
Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment
Chung, P. J., Song, C., Deek, J., Miller, H. P., Li, Y., Choi, M. C., Wilson, L., Feinstein, S. C., & Safinya, C. R. (2016) · Nature Communications · doi:10.1038/ncomms12278 · Cited by 65 · see citing works
Comprehensive Quantitative Profiling of Tau and Phosphorylated Tau Peptides in Cerebrospinal Fluid by Mass Spectrometry Provides New Biomarker Candidates
Russell, C. L., Mitra, V., Hansson, K., Blennow, K., Gobom, J., Zetterberg, H., Hiltunen, M., Ward, M., & Pike, I. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-160633 · Cited by 52 · see citing works
Faculty Opinions recommendation of Tau kinetics in neurons and the human central nervous system.
Millan, M. J. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732876856.793545483 · Cited by 1 · see citing works

Flagged first, then by citations

Sorted by citations

Blood 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
Self-citation
Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer’s continuum when only subtle changes in Aβ pathology are detected
Suárez‐Calvet, M., Karikari, T. K., Ashton, N. J., Lantero Rodríguez, J., Milà‐Alomà, M., Gispert, J. D., Salvadó, G., Minguillon, C., Fauria, K., Shekari, M., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.202012921 · Cited by 401 · see citing works
Tau-targeting therapies for Alzheimer disease: Current status and future directions
Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00883-2 · Cited by 371 · see citing works
Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease
Arnsten, A. F. T., Datta, D., Del Tredici, K., & Braak, H. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12192 · Cited by 361 · see citing works
Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive tau PET in Alzheimer's disease
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 · see citing works
Comparison of Plasma Phosphorylated Tau Species With Amyloid and Tau Positron Emission Tomography, Neurodegeneration, Vascular Pathology, and Cognitive Outcomes
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
Cerebrospinal fluid phospho-tau T217 outperforms T181 as a biomarker for the differential diagnosis of Alzheimer's disease and PET amyloid-positive patient identification
Barthélemy, N. R., Bateman, R. J., Hirtz, C., Marin, P., Becher, F., Sato, C., Gabelle, A., & Lehmann, S. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00596-4 · Cited by 229 · see citing works
Self-citation
“Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies
Xia, Y., Prokop, S., & Giasson, B. I. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00460-5 · Cited by 218 · see citing works
CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer’s disease
Horie, K., Barthélemy, N. R., Sato, C., & Bateman, R. J. (2021) · Brain · doi:10.1093/brain/awaa373 · Cited by 180 · see citing works
Self-citation
Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Current Evidence and Future Perspectives
McGrowder, D. A., Miller, F. G., Vaz, K., Nwokocha, C. R., Wilson-Clarke, C. F., Anderson, M., Brown, J., Anderson-Jackson, L., Williams, L., Latore, L., et al. (2021) · Brain Sciences · doi:10.3390/brainsci11020215 · Cited by 167 · see citing works
CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer’s disease
Barthélemy, N. R., Saef, B., Li, Y., Gordon, B. A., He, Y., Horie, K., Stomrud, E., Salvadó, G., Janelidze, S., Sato, C., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00380-7 · Cited by 153 · see citing works
Self-citation
Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis
Karikari, T. K., Emeršič, A., Vrillon, A., Lantero‐Rodriguez, J., Ashton, N. J., Kramberger, M. G., Dumurgier, J., Hourregue, C., Čučnik, S., Brinkmalm, G., et al. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12236 · Cited by 143 · see citing works
Mass spectrometric simultaneous quantification of tau species in plasma shows differential associations with amyloid and tau pathologies.
Montoliu-Gaya, L., Benedet, A. L., Tissot, C., Vrillon, A., Ashton, N. J., Brum, W. S., Lantero-Rodriguez, J., Stevenson, J., Nilsson, J., Sauer, M., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00405-1 · Cited by 122 · see citing works
Sleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid
Barthélemy, N. R., Liu, H., Lu, W., Kotzbauer, P. T., Bateman, R. J., & Lucey, B. P. (2020) · Annals of Neurology · doi:10.1002/ana.25702 · Cited by 128 · see citing works
Self-citation
Comparing the clinical utility and diagnostic performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays
Leuzy, A., Janelidze, S., Mattsson-Carlgren, N., Palmqvist, S., Jacobs, D., Cicognola, C., Stomrud, E., Vanmechelen, E., Dage, J. L., & Hansson, O. (2021) · Neurology · doi:10.1212/wnl.0000000000012727 · Cited by 128 · see citing works
Tau Ser208 phosphorylation promotes aggregation and reveals neuropathologic diversity in Alzheimer’s disease and other tauopathies
Xia, Y., Prokop, S., Gorion, K.-M. M., Kim, J. D., Sorrentino, Z. A., Bell, B. M., Manaois, A. N., Chakrabarty, P., Davies, P., & Giasson, B. I. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00967-w · Cited by 114 · see citing works
The informed road map to prevention of Alzheimer Disease: a call to arms
McDade, E., Llibre-Guerra, J. J., Holtzman, D. M., Morris, J. C., & Bateman, R. J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00467-y · Cited by 89 · see citing works
Self-citation
Suvorexant Acutely Decreases Tau Phosphorylation and Aβ in the Human CNS
Lucey, B. P., Liu, H., Toedebusch, C. D., Freund, D., Redrick, T., Chahin, S. L., Mawuenyega, K. G., Bollinger, J. G., Ovod, V., Barthélemy, N. R., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26641 · Cited by 106 · see citing works
Self-citation
Age‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates
Datta, D., Leslie, S. N., Wang, M., Morozov, Y. M., Yang, S., Mentone, S., Zeiss, C. J., Duque, A., RAKIC, P. T., Horváth, T. L., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12325 · Cited by 98 · see citing works
Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification
Izzo, N. J., Yuede, C. M., Mozzoni, K., Limegrover, C. S., Rehak, C., Yurko, R., Waybright, L., Look, G. C., Rishton, G. M., Safferstein, H., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12302 · Cited by 101 · see citing works
Specific post-translational modifications of soluble tau protein distinguishes Alzheimer’s disease and primary tauopathies
Zola, N. K. N., Balty, C., Ruys, S. P. D., Vanparys, A., Huyghe, N. D., Herinckx, G., Johanns, M., Boyer, E., Kienlen‐Campard, P., Rider, M. H., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39328-1 · Cited by 93 · see citing works
Plasma p‐tau immunoassays in clinical research for Alzheimer's disease
Teunissen, C. E., Kolster, R., Triana‐Baltzer, G., Janelidze, S., Zetterberg, H., & Kolb, H. C. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14397 · Cited by 92 · see citing works
Tauopathies: Deciphering Disease Mechanisms to Develop Effective Therapies
Silva, M. C., & Haggarty, S. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21238948 · Cited by 87 · see citing works
Acute sleep loss decreases CSF‐to‐blood clearance of Alzheimer's disease biomarkers
Liu, H., Barthélemy, N. R., Ovod, V., Bollinger, J. G., He, Y., Chahin, S. L., Androff, B., Bateman, R. J., & Lucey, B. P. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.12930 · Cited by 86 · see citing works
Self-citation
Natural Therapeutics in Aid of Treating Alzheimer’s Disease: A Green Gateway Toward Ending Quest for Treating Neurological Disorders
Bhat, B. A., Almilaibary, A., Mir, R. A., Aljarallah, B. M., Mir, W. R., Ahmad, F., & Mir, M. A. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.884345 · Cited by 85 · see citing works
P-tau217 as a Reliable Blood-Based Marker of Alzheimer’s Disease
Lai, R., Li, B., & Bishnoi, R. J. (2024) · Biomedicines · doi:10.3390/biomedicines12081836 · Cited by 81 · see citing works
Alzheimer’s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer’s disease
Arnsten, A. F. T., Datta, D., Leslie, S., Yang, S.-T., Wang, M., & Nairn, A. C. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903671116 · Cited by 74 · see citing works
Latest advances in cerebrospinal fluid and blood biomarkers of Alzheimer’s disease
Milà‐Alomà, M., Suárez‐Calvet, M., & Molinuevo, J. L. (2019) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756286419888819 · Cited by 78 · see citing works
Introduction of Tau Oligomers into Cortical Neurons Alters Action Potential Dynamics and Disrupts Synaptic Transmission and Plasticity
Hill, E., Karikari, T. K., Moffat, K. G., Richardson, M. J. E., & Wall, M. J. (2019) · eNeuro · doi:10.1523/eneuro.0166-19.2019 · Cited by 77 · see citing works
Mass spectrometry‐based methods for robust measurement of Alzheimer's disease biomarkers in biological fluids
Korecka, M., & Shaw, L. M. J. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15465 · Cited by 79 · see citing works
Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain
Moloney, C. M., Labuzan, S. A., Crook, J. E., Siddiqui, H., Castanedes‐Casey, M., Lachner, C., Petersen, R. C., Duara, R., Graff‐Radford, N. R., Dickson, D. W., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12749 · Cited by 74 · see citing works
CSF p-tau205: a biomarker of tau pathology in Alzheimer’s disease
Lantero‐Rodriguez, J., Montoliu‐Gaya, L., Benedet, A. L., Vrillon, A., Dumurgier, J., Cognat, E., Brum, W. S., Rahmouni, N., Stevenson, J., Servaes, S., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-023-02659-w · Cited by 70 · see citing works
Significance of Blood and Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Sensitivity, Specificity and Potential for Clinical Use
d’Abramo, C., D'adamio, L., & Giliberto, L. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030116 · Cited by 68 · see citing works
Regional correlation of biochemical measures of amyloid and tau phosphorylation in the brain
Horie, K., Barthélemy, N. R., Mallipeddi, N., Li, Y., Franklin, E. E., Perrin, R. J., Bateman, R. J., & Sato, C. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01019-z · Cited by 62 · see citing works
Self-citation
Biofluid Biomarkers of Alzheimer’s Disease: Progress, Problems, and Perspectives
Huang, S., Wang, Y.-J., & Guo, J.-H. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00836-7 · Cited by 52 · see citing works
Comparison of CSF phosphorylated tau 181 and 217 for cognitive decline
Mielke, M. M., Aakre, J. A., Algeciras‐Schimnich, A., Proctor, N. K., Machulda, M. M., Eichenlaub, U., Knopman, D. S., Vemuri, P., Graff‐Radford, J., Jack, C. R., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12415 · Cited by 55 · see citing works
The AD tau core spontaneously self-assembles and recruits full-length tau to filaments
Carlomagno, Y., Manne, S., Deture, M. A., Prudencio, M., Zhang, Y., Al‐Shaikh, R. H., Dunmore, J. A., Daughrity, L. M., Song, Y., Castanedes‐Casey, M., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108843 · Cited by 57 · see citing works
Antibody-free measurement of cerebrospinal fluid tau phosphorylation across the Alzheimer’s disease continuum
Gobom, J., Benedet, A. L., Mattsson, N., Montoliu‐Gaya, L., Schultz, N., Ashton, N. J., Janelidze, S., Servaes, S., Sauer, M., Pascoal, T. A., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00586-0 · Cited by 57 · see citing works
Biomarkers of Alzheimer Disease
Budelier, M. M., & Bateman, R. J. (2019) · The Journal of Applied Laboratory Medicine · doi:10.1373/jalm.2019.030080 · Cited by 57 · see citing works
Self-citation
P‐tau235: a novel biomarker for staging preclinical Alzheimer’s disease
Lantero‐Rodriguez, J., Snellman, A., Benedet, A. L., Milà‐Alomà, M., Camporesi, E., Montoliu‐Gaya, L., Ashton, N. J., Vrillon, A., Karikari, T. K., Gispert, J. D., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202115098 · Cited by 54 · see citing works
Brain Tissue-Derived Extracellular Vesicles in Alzheimer’s Disease Display Altered Key Protein Levels Including Cell Type-Specific Markers
Huang, Y., Driedonks, T. A. P., Cheng, L., Turchinovich, A., Rajapaksha, H., Arab, T., Powell, B. H., Pletniková, O., Redding‐Ochoa, J., Troncoso, J. C., et al. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220322 · Cited by 55 · see citing works
Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias
Hanes, J., Kováč, A., Kvartsberg, H., Kontseková, E., Fialová, Ľ., Katina, S., Kováčech, B., Stevens, E., Hort, J., Vyhnálek, M., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000010814 · Cited by 54 · see citing works
A map of neurofilament light chain species in brain and cerebrospinal fluid and alterations in Alzheimer’s disease
Budelier, M. M., He, Y., Barthélemy, N. R., Jiang, H., Li, Y., Park, E., Henson, R. L., Schindler, S. E., Holtzman, D. M., & Bateman, R. J. (2022) · Brain Communications · doi:10.1093/braincomms/fcac045 · Cited by 53 · see citing works
Self-citation
A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications
Drepper, F., Biernat, J., Kaniyappan, S., Meyer, H. E., Mandelkow, E., Warscheid, B., & Mandelkow�, E. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.015882 · Cited by 53 · see citing works
Proteoforms and their expanding role in laboratory medicine
Forgrave, L. M., Wang, M., Yang, D., & DeMarco, M. L. (2021) · Practical Laboratory Medicine · doi:10.1016/j.plabm.2021.e00260 · Cited by 46 · see citing works
Rapamycin treatment for Alzheimer’s disease and related dementias: a pilot phase 1 clinical trial
Gonzales, M. M., Garbarino, V. R., Kautz, T. F., Song, X., Lopez‐Cruzan, M., Linehan, L. A., Skike, C. E. V., de Erausquin, G. A., Galván, V., Orr, M. E., et al. (2025) · Communications Medicine · doi:10.1038/s43856-025-00904-9 · Cited by 56 · see citing works
Self-citation
Perspectives in fluid biomarkers in neurodegeneration from the 2019 biomarkers in neurodegenerative diseases course—a joint PhD student course at University College London and University of Gothenburg
Obrocki, P., Khatun, A., Ness, D., Senkevich, K. A., Hanrieder, J., Capraro, F., Mattsson, N., Andréasson, U., Portelius, E., Ashton, N. J., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00586-6 · Cited by 51 · see citing works
Alzheimer Disease
McDade, E. (2022) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001131 · Cited by 49 · see citing works
Vascular smooth muscle cell dysfunction contribute to neuroinflammation and Tau hyperphosphorylation in Alzheimer disease
Aguilar-Pineda, J. A., Vera-López, K. J., Shrivastava, P., Chávez‐Fumagalli, M. Á., Nieto-Montesinos, R., Alvarez, K. L. F., Goyzueta-Mamani, L. D., Dávila-Del-Carpio, G., Gómez, B., Miller, C. L., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102993 · Cited by 44 · see citing works
Disentangling tau: One protein, many therapeutic approaches
Lane‐Donovan, C., & Boxer, A. L. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00321 · Cited by 44 · see citing works
Plasma N-terminal containing tau fragments (NTA-tau): a biomarker of tau deposition in Alzheimer’s Disease
Lantero‐Rodriguez, J., Salvadó, G., Snellman, A., Montoliu‐Gaya, L., Brum, W. S., Benedet, A. L., Mattsson, N., Tideman, P., Janelidze, S., Palmqvist, S., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00707-x · Cited by 42 · see citing works
Mass Spectrometry for Neurobiomarker Discovery: The Relevance of Post-Translational Modifications
Azevedo, R., Jacquemin, C., Villain, N., Fenaille, F., Lamari, F., & Bécher, F. (2022) · Cells · doi:10.3390/cells11081279 · Cited by 42 · see citing works
Targeting tau only extracellularly is likely to be less efficacious than targeting it both intra- and extracellularly
Congdon, E. E., Jiang, Y., & Sigurdsson, E. M. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.12.002 · Cited by 37 · see citing works
Intermediate flortaucipir uptake is associated with Aβ-PET and CSF tau in asymptomatic adults
McSweeney, M., Binette, A. P., Meyer, P., Gonneaud, J., Bedetti, C., Ozlen, H., Labonté, A., Rosa‐Neto, P., Breitner, J. C. S., Poirier, J., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000008905 · Cited by 37 · see citing works
The ‘a, b, c’s of pretangle tau and their relation to aging and the risk of Alzheimer’s Disease
Harley, C. W., Walling, S. G., Yuan, Q., & Martin, G. M. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.12.010 · Cited by 39 · see citing works
Tau protein profiling in tauopathies: a human brain study
Lantero‐Rodriguez, J., Camporesi, E., Montoliu‐Gaya, L., Gobom, J., Piotrowska, D., Olsson, M., Matečko‐Burmann, I., Becker, B., Brinkmalm, A., Burmann, B. M., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00741-9 · Cited by 38 · see citing works
Another step forward in blood-based diagnostics for Alzheimer’s disease
Bateman, R. J., Barthélemy, N. R., & Horie, K. (2020) · Nature Medicine · doi:10.1038/s41591-020-0797-4 · Cited by 37 · see citing works
Self-citation
Current and future applications of induced pluripotent stem cell-based models to study pathological proteins in neurodegenerative disorders
Jacquet, A. D. R., Denis, H. L., Cicchetti, F., & Alpaugh, M. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00999-7 · Cited by 35 · see citing works
Neuroprotective effect of nose-to-brain delivery of Asiatic acid in solid lipid nanoparticles and its mechanisms against memory dysfunction induced by Amyloid Beta1-42 in mice
Islamie, R., Myint, S. L. L., Rojanaratha, T., Ritthidej, G. C., Wanakhachornkrai, O., Wattanathamsan, O., & Rodsiri, R. (2023) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-023-04125-2 · Cited by 35 · see citing works
Site-Specific Cerebrospinal Fluid Tau Hyperphosphorylation in Response to Alzheimer’s Disease Brain Pathology: Not All Tau Phospho-Sites are Hyperphosphorylated
Barthélemy, N. R., Toth, B., Manser, P. T., Sanabria-Bohórquez, S., Teng, E., Keeley, M., Bateman, R. J., Weimer, R. M., & Wildsmith, K. R. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210677 · Cited by 33 · see citing works
Self-citation
Phase 1 Studies of the Anti-Tau Monoclonal Antibody JNJ-63733657 in Healthy Participants and Participants with Alzheimer's Disease
Galpern, W. R., Triana‐Baltzer, G., Li, L., Kolen, K. V., Timmers, M., Haeverans, K., Janssens, L., Kolb, H. C., Nandy, P., Aida, K., et al. (2024) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2024.163 · Cited by 38 · see citing works
Development of molecular tools for diagnosis of Alzheimer’s disease that are based on detection of amyloidogenic proteins
Kulichikhin, K. Y., Fedotov, S. A., Rubel, M. S., Zalutskaya, N. M., Zobnina, A. E., Malikova, O. A., Незнанов, Н. Г., Chernoff, Y. O., & Rubel, A. A. (2021) · Prion · doi:10.1080/19336896.2021.1917289 · Cited by 33 · see citing works
Clinical utility of cerebrospinal fluid biomarkers measured by LUMIPULSE ® system
Nojima, H., Itō, S., Kushida, A., Abe, A., Motsuchi, W., Verbel, D., Vandijck, M. L. J., Jannes, G., Vandenbroucke, I., & Aoyagi, K. (2022) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51681 · Cited by 30 · see citing works
Amyloid, tau and risk of Alzheimer’s disease: a Mendelian randomization study
Yeung, C. H. C., Lau, K. W. D., Yeung, S. L. A., & Schooling, C. M. (2020) · European Journal of Epidemiology · doi:10.1007/s10654-020-00683-8 · Cited by 27 · see citing works
Immunoassay detection of multiphosphorylated tau proteoforms as cerebrospinal fluid and plasma Alzheimer’s disease biomarkers
Wojdała, A. L., Bellomo, G., Gaetani, L., Teunissen, C. E., Parnetti, L., & Chiasserini, D. (2025) · Nature Communications · doi:10.1038/s41467-024-54878-8 · Cited by 29 · see citing works
Selective Detection of Misfolded Tau From Postmortem Alzheimer’s Disease Brains
Wu, L., Wang, Z., Lad, S., Gilyazova, N., Dougharty, D. T., Marcus, M., Henderson, F. E., Ray, W. K., Siedlak, S. L., Li, J., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.945875 · Cited by 26 · see citing works
Comparison of cerebrospinal fluid, plasma and neuroimaging biomarker utility in Alzheimer’s disease
Meeker, K. L., Luckett, P. H., Barthélemy, N. R., Hobbs, D. A., Chen, C. D., Bollinger, J., Ovod, V., Flores, S. E., Keefe, S., Henson, R. L., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae081 · Cited by 27 · see citing works
Self-citation
Defined Tau Phosphospecies Differentially Inhibit Fast Axonal Transport Through Activation of Two Independent Signaling Pathways
Morris, S. L., Tsai, M.-Y., Aloe, S., Bechberger, K., König, S., Morfini, G. A., & Brady, S. T. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.610037 · Cited by 25 · see citing works
Development of immunoprecipitation – two-dimensional liquid chromatography – mass spectrometry methodology as biomarker read-out to quantify phosphorylated tau in cerebrospinal fluid from Alzheimer disease patients
Bijttebier, S., Theunis, C., Jahouh, F., Martins, D. R., Verhemeldonck, M., Grauwen, K., Dillen, L., & Mercken, M. H. (2021) · Journal of Chromatography A · doi:10.1016/j.chroma.2021.462299 · Cited by 24 · see citing works
A neurodegeneration checkpoint mediated by REST protects against the onset of Alzheimer’s disease
Aron, L., Qiu, C., Ngian, Z., Liang, M., Drake, D., Choi, J., Fernandez, M. A., Roche, P., Bunting, E. L., Lacey, E. K., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42704-6 · Cited by 22 · see citing works
Liquid chromatography-tandem mass spectrometry in clinical laboratory protein measurement
Ma, Y., Wang, D., Li, H., Ma, X., Zou, Y., Mu, D., Yu, S., Cheng, X., & Qiu, L. (2024) · Clinica Chimica Acta · doi:10.1016/j.cca.2024.119846 · Cited by 22 · see citing works
MAPT R406W increases tau T217 phosphorylation in absence of amyloid pathology
Sato, C., Mallipeddi, N., Ghoshal, N., Wright, B. A., Day, G. S., Davis, A. A., Kim, A. H., Zipfel, G. J., Bateman, R. J., Gabelle, A., et al. (2021) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51435 · Cited by 21 · see citing works
Self-citation
Uncommon posttranslational modifications in proteomics: ADP‐ribosylation, tyrosine nitration, and tyrosine sulfation
Bashyal, A., & Brodbelt, J. S. (2022) · Mass Spectrometry Reviews · doi:10.1002/mas.21811 · Cited by 22 · see citing works
Tau kinetics in Alzheimer's disease
Hier, D. B., Azizi, S., Thimgan, M. S., & Wunsch, D. C. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1055170 · Cited by 21 · see citing works
Development and Validation of a High Sensitivity Assay for Measuring p217 + tau in Cerebrospinal Fluid
Triana‐Baltzer, G., Kolen, K. V., Theunis, C., Moughadam, S., Slemmon, R., Mercken, M. H., Galpern, W. R., Sun, H. F., & Kolb, H. C. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200463 · Cited by 21 · see citing works
Current Progress and Future Directions for Tau-Based Fluid Biomarker Diagnostics in Alzheimer’s Disease
Arastoo, M., Lofthouse, R. A., Penny, L. K., Harrington, C. R., Porter, A., Wischik, C. M., & Palliyil, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228673 · Cited by 21 · see citing works
CSF Tau phosphorylation at Thr205 is associated with loss of white matter integrity in autosomal dominant Alzheimer disease
Strain, J. F., Barthélemy, N. R., Horie, K., Gordon, B. A., Kilgore, C. B., Aschenbrenner, A. J., Cruchaga, C., Xiong, C., Joseph‐Mathurin, N., Hassenstab, J. J., et al. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105714 · Cited by 20 · see citing works
Self-citation
Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases
Zhang, S.-Q., Dong, H., Bian, J., Li, D., & Liu, C. (2022) · Fundamental Research · doi:10.1016/j.fmre.2022.10.009 · Cited by 20 · see citing works
Identification of cis-acting determinants mediating the unconventional secretion of tau
Katsinelos, T., McEwan, W. A., Jahn, T. R., & Nickel, W. (2021) · Scientific Reports · doi:10.1038/s41598-021-92433-3 · Cited by 16 · see citing works
Highly Specific and Sensitive Target Binding by the Humanized pS396-Tau Antibody hC10.2 Across a Wide Spectrum of Alzheimer’s Disease and Primary Tauopathy Postmortem Brains
Helboe, L., Rosenqvist, N., Volbracht, C., Pedersen, L. Ø., Pedersen, J. T., Christensen, S., Egebjerg, J., Christoffersen, C. T., Bang‐Andersen, B., Beach, T. G., et al. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220125 · Cited by 20 · see citing works
Alzheimer's Disease Biomarker Analysis Using Targeted Mass Spectrometry
Gobom, J., Brinkmalm, A., Brinkmalm, G., Blennow, K., & Zetterberg, H. (2024) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2024.100721 · Cited by 18 · see citing works
Pilot Study for Deciphering Post-Translational Modifications and Proteoforms of Tau Protein by Capillary Electrophoresis-Mass Spectrometry
Fang, F., Xu, T., Hagar, H. C., Hovde, S., Kuo, M., & Sun, L. (2024) · Journal of Proteome Research · doi:10.1021/acs.jproteome.4c00587 · Cited by 17 · see citing works
Amyloid PET detects the deposition of brain Aβ earlier than CSF fluid biomarkers
Lowe, V. J., Mester, C. T., Lundt, E. S., Lee, J., Ghatamaneni, S., Algeciras‐Schimnich, A., Campbell, M. R., Graff‐Radford, J., Nguyen, A. T., Min, H.-K. P., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14317 · Cited by 19 · see citing works
Proteomics Landscape of Alzheimer’s Disease
Jain, A., & Sathe, G. J. (2021) · Proteomes · doi:10.3390/proteomes9010013 · Cited by 18 · see citing works
Tau: a biomarker of Huntington’s disease
Lepinay, E., & Cicchetti, F. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02230-9 · Cited by 18 · see citing works
Separation of Isomeric Tau Phosphopeptides from Alzheimer’s Disease Brain by Cyclic Ion Mobility Mass Spectrometry
Kováč, A., Majerová, P., Nytka, M., Cechová, M. Z., Bednář, P., Hájek, R., Cooper-Shepherd, D. A., Muck, A., & Lemr, K. (2023) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.2c00289 · Cited by 16 · see citing works
High-specificity antibodies and detection methods for quantifying phosphorylated tau from clinical samples
Arbaciauskaite, M., Yu, L., & Cho, Y. K. (2021) · Antibody Therapeutics · doi:10.1093/abt/tbab004 · Cited by 16 · see citing works
Recent Advances in Mass Spectrometry-Based Studies of Post-Translational Modifications in Alzheimer’s Disease
Wu, F., Li, W., Lu, H., & Li, L. (2025) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2025.101003 · Cited by 16 · see citing works
A Quantitative LC-MS/MS Method for Distinguishing the Tau Protein Forms Phosphorylated and Nonphosphorylated at Serine-396
Jacobsen, A., van de Merbel, N. C., Ditlevsen, D. K., Tvermosegaard, K., Schalk, F., Lambert, W., Bundgaard, C., Pedersen, J. T., & Rosenqvist, N. (2023) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.2c00324 · Cited by 15 · see citing works
Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts
Lantero‐Rodriguez, J., Vrillon, A., Fernández‐Lebrero, A., Ortiz‐Romero, P., Snellman, A., Montoliu‐Gaya, L., Brum, W. S., Cognat, E., Dumurgier, J., Puig‐Pijoan, A., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01201-0 · Cited by 14 · see citing works
Biomarker-related phospho-tau217 appears in synapses around Aβ plaques prior to tau tangle in cerebral cortex of preclinical Alzheimer’s disease
Hirota, Y., Sakakibara, Y., Morishima, M., Sano, T., Hara, M., Arakawa, A., Takao, M., Murayama, S., Saito, Y., Sekiya, M., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116203 · Cited by 13 · see citing works
Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
Leslie, S. N., Kanyo, J. E., Datta, D., Wilson, R. S., Zeiss, C. J., Duque, A., Lam, T. T., Arnsten, A. F. T., & Nairn, A. C. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.767322 · Cited by 13 · see citing works
Mass spectrometry analysis of tau and amyloid‐beta in iPSC‐derived models of Alzheimer’s disease and dementia
Arber, C., Alatza, A., Leckey, C. A., Paterson, R. W., Zetterberg, H., & Wray, S. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15315 · Cited by 12 · see citing works
Evaluating Spatiotemporal Dynamics of Phosphorylation of RNA Polymerase II Carboxy-Terminal Domain by Ultraviolet Photodissociation Mass Spectrometry
Escobar, E. E., Ramani, M. K. V., Zhang, Y., & Brodbelt, J. S. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c03321 · Cited by 13 · see citing works
Detecting the Undetectable: Advances in Methods for Identifying Small Tau Aggregates in Neurodegenerative Diseases
Böken, D., Wu, Y., Zhang, Z.-W., & Klenerman, D. (2024) · ChemBioChem · doi:10.1002/cbic.202400877 · Cited by 10 · see citing works
Tau phosphorylation at Alzheimer's disease biomarker sites impairs its cleavage by lysosomal proteases
Lane‐Donovan, C., Smith, A. W., Saloner, R., Miller, B. L., Casaletto, K. B., & Kao, A. W. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70320 · Cited by 12 · see citing works
Variant biomarker discovery using mass spectrometry-based proteogenomics
Reilly, L., Seddighi, S., Singleton, A., Cookson, M., Ward, M., & Qi, Y. A. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1191993 · Cited by 11 · see citing works
O-GlcNAc modification differentially regulates microtubule binding and pathological conformations of tau isoforms in vitro
Alhadidy, M. M., Stemmer, P. M., & Kanaan, N. M. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108263 · Cited by 11 · see citing works
Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry study
Santiago, J., Pocevičiūtė, D., Vogel, J. W., Bank, T. N. B., Brinkmalm, G., & Wennström, M. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107057 · Cited by 12 · see citing works
Targeting tau in Alzheimer’s Disease: rationale, approach and challenges
Aslanyan, A., Foiani, M. S., Giovannucci, T. A., McDade, E., Duff, K., Mummery, C. J., Schöll, M., Wildsmith, K. R., & Paterson, R. W. (2026) · Molecular Neurodegeneration · doi:10.1186/s13024-026-00925-5 · Cited by 10 · see citing works

O1‐01‐02: TAU PHOSPHORYLATION RATES CHANGE FROM BRAIN TO CEREBROSPINAL FLUID AND ARE DIFFERENTIALLY AFFECTED BY ALZHEIMER DISEASE
Barthélemy, N. R., Mallipeddi, N., Sato, C., & Bateman, R. J. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.06.4518
Self-citation
P2‐160: The use of mass spectrometry for multisite phosphorylation assays for tau protein
Schofield, E., Ward, M. A., Ocaña, M. F., Killick, R., Hanger, D. P., Byers, H. L., Lovestone, S., & Anderton, B. H. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.05.1234
P4‐234: Mass spectrometry follow‐up of t181, s199, s202, t205, and T217 tau phosphorylation in cerebrospinal fluid from patients revealed a specific Alzheimer's disease pattern
Barthélemy, N. R., Hirtz, C., Schraen‐Maschke, S., Sevéno, M., Bateman, R. J., Marin, P., Bécher, F., Gabelle, A., & Lehmann, S. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.08.063 · Cited by 4 · see citing works
Self-citation
Comprehensive Quantitative Profiling of Tau and Phosphorylated Tau Peptides in Cerebrospinal Fluid by Mass Spectrometry Provides New Biomarker Candidates
Russell, C. L., Mitra, V., Hansson, K., Blennow, K., Gobom, J., Zetterberg, H., Hiltunen, M., Ward, M., & Pike, I. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-160633 · Cited by 52 · see citing works
O5‐05‐06: Discovery of multiple phosphorylated tau biomarkers in CSF using a novel mass spectrometry method
Russell, C., Mitra, V., Hiltunen, M. O., Zetterberg, H., Ward, M. A., & Pike, I. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.07.474

Authors: Barthélemy, N. R., Mallipeddi, N., Moiseyev, P., Sato, C., & Bateman, R. J.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Barthélemy, Nicolas R.
Bateman, Randall J.
ORCID: Barthélemy, Nicolas R.
Mallipeddi, Nipun
Sato, Chihiro
Bateman, Randall J.
Venue: Frontiers in Aging Neuroscience
Publisher: Frontiers Media SA
Published: 2019-05-21
Volume: 11
Pages: 121-121
ISSN: 1663-4365 (ISSN-L)
DOI: 10.3389/fnagi.2019.00121
PMC: PMC6537657
OpenAlex: W2945823364
Cited by: 152
References: 34
Citations by year: 2026: 10 · 2025: 15 · 2024: 24 · 2023: 19 · 2022: 22 · 2021: 32 · 2020: 25 · 2019: 5
FWCI: 14.41
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Aging Neuroscience (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Alzheimer’s Association (AARF-16-443265)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: tau phosphorylation, Alzheimer's disease, cerebrospinal fluid, brain, parallel reaction monitoring, tau phosphorylation sites, neurofibrillary tangles, tau isoforms, AT8 antibody, Braak stages, biomarkers, tau aggregation, site-specific phosphorylation, targeted mass spectrometry

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

Tau Phosphorylation Rates Measured by Mass Spectrometry Differ in the Intracellular Brain vs. Extracellular Cerebrospinal Fluid Compartments and Are Differentially Affected by Alzheimer’s Disease

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks