Correlation of cerebrospinal fluid levels of Tau protein phosphorylated at threonine 231 with rates of hippocampal atrophy in Alzheimer disease
Abstract
Background The microtubule-associated tau protein abnormally phosphorylated at threonine 231 (p-tau231) has been investigated as a potential marker of Alzheimer disease. Levels of cerebrospinal fluid (CSF) p-tau231 vary across patients with Alzheimer disease. We hypothesized that these variations partially reflect differences in the degree of neuronal damage and therefore may be used to predict structural disease progression. Objective To investigate whether CSF p-tau231 levels correlate with rates of hippocampal atrophy as an in vivo marker of regional neuronal loss. Design and patients We measured hippocampal volumes on the basis of serial magnetic resonance image examinations in 22 patients with Alzheimer disease. In addition, we determined CSF p-tau231 levels at baseline. Results Levels of CSF p-tau231 were significantly correlated with baseline hippocampal volumes (P Conclusion These findings suggest that variations in p-tau231 levels may be used to predict progression of brain atrophy in patients with Alzheimer disease.
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No significant effect of T-tau level on hippocampal atrophy was reported.
“The same study has also reported, no significant effect of T-tau level on hippocampal atrophy (Hampel et al., 2005).”
From T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease (2015) · cites this paper as Hampel et al., 2005
Increased CSF tau level corresponds to higher baseline hippocampal volume in AD.
“It has been shown that the increased CSF tau level corresponds to the higher baseline hippocampal volume in AD.”
From T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease (2015) · cites this paper as Hampel et al., 2005
Cites
Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space
Collins, D. L., Neelin, P., Peters, T. M., & Evans, A. C. (1994) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199403000-00005 · Cited by 3,431 · cited 1× · see citing works
“Before volumetric measurements, a transformation algorithm was used to align MRIs between time points.(11) First, for each patient the second (and for 2 patients, the third) MRI was aligned to the first MRI in the series using a 6-parameter rigid body transformation.”
MethodSelf-citationRates of hippocampal atrophy correlate with change in clinical status in aging and AD
Jack, C. R., Petersen, R. C., Xu, Y., O’Brien, P. C., Smith, G. E., Ivnik, R. J., Boeve, B. F., Tangalos, E. G., & Kokmen, E. (2000) · Neurology · doi:10.1212/wnl.55.4.484 · Cited by 937 · see citing works
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The clinical use of structural MRI in Alzheimer disease
Frisoni, G. B., Fox, N. C., Jack, C. R., Scheltens, P., & Thompson, P. M. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.215 · Cited by 2,113 · see citing works
Revising the definition of Alzheimer's disease: a new lexicon
Dubois, B., Feldman, H. H., Jacova, C., Cummings, J. L., DeKosky, S. T., Barberger-Gateau, P., Delacourte, A., Frisoni, G., Fox, N. C., Galasko, D., et al. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70223-4 · Cited by 1,869 · see citing works
Self-citationCerebrospinal fluid and plasma biomarkers in Alzheimer disease
Blennow, K., Hampel, H., Weiner, M., & Zetterberg, H. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.4 · Cited by 1,863 · see citing works
Self-citationPlasma 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
Schuff, N., Woerner, N., Boreta, L., Kornfield, T., Shaw, L. M., Trojanowski, J. Q., Thompson, P. M., Jack, C. R., Weiner, M. W., & Initiative, T. A. D. N. (2008) · Brain · doi:10.1093/brain/awp007 · Cited by 679 · see citing works
“Lastly, few studies so far reported findings of hippocampal changes, ApoE and CSF biomarkers together (Hampel et al., 2005; de Leon et al., 2006; Fjell et al., 2008).”
Buerger, K., Ewers, M., Pirttila, T., Zinkowski, R., Alafuzoff, I., Teipel, S. J., DeBernardis, J., Kerkman, D., McCulloch, C., Soininen, H., et al. (2006) · Brain · doi:10.1093/brain/awl269 · Cited by 586 · see citing works
“…atrophy Downloaded from https://academic.oup.com/brain/article-abstract/129/11/3035/293326 by guest on 29 July 2018 as measured with serial magnetic resonance imaging (Hampel et al., 2005) suggesting that CSF P-tau231 may correlate with allocortical changes when measured in a longitudinal design.”
MethodSelf-citationWang, J., Xia, Y., Grundke, I., & Iqbal, K. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129031 · Cited by 530 · see citing works
“The concentrations of total tau and phosphorylated tau in cerebrospinal fluid are strongly associated with the future development of AD in patients with mild cognitive impairment [109, 110], which suggests that hyperphosphorylated tau may serve as a predictor of AD.”
BackgroundLongitudinal Change in CSF Biomarkers in Autosomal-Dominant Alzheimer’s Disease
Fagan, A. M., Xiong, C., Jasielec, M. S., Bateman, R. J., Goate, A. M., Benzinger, T. L. S., Ghetti, B., Martins, R. N., Masters, C. L., Mayeux, R., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007901 · Cited by 434 · see citing works
“Blankenstein, Standardization of assay procedures for analysis of the CSF biomarkers amyloid b(1-42), tau, and phosphorylated tau in Alzheimer’s disease: Report of an international workshop.”
BackgroundMethodA meta-analysis of hippocampal atrophy rates in Alzheimer's disease
Barnes, J., Bartlett, J. W., van de Pol, L. A., Loy, C. T., Scahill, R. I., Frost, C. D., Thompson, P. M., & Fox, N. C. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.01.010 · Cited by 396 · see citing works
“, 2004, 2007a), three did not report annualised atrophy rate (Laakso et al., 2000; Krishnan et al., 2003; Hampel et al., 2005) and two included patients with Vascular Dementia (Cardenas et al.”
BackgroundThambisetty, M., Simmons, A., Velayudhan, L., Hye, A., Campbell, J., Zhang, Y., Wahlund, L.-O., Westman, E., Kinsey, A., Güntert, A., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.78 · Cited by 405 · see citing works
“Moreover, decreased hippocampal volume in AD patients is associated with neuronal loss, confirming its validity as a marker of neurodegeneration.(35) A second independent outcome variable in the discovery-phase studies was rate of cognitive decline, derived as a measure of decrease in the ADAScog scores during a 6-mon…”
Self-citationMicrotubule-associated protein tau in development, degeneration and protection of neurons
Wang, J., & Liu, F. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.03.002 · Cited by 395 · see citing works
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
“…NfL, neurofilament light; N, N-terminal; p-tau, phosphorylated tau; t-tau, total tau. ª 2020 The Authors EMBO Molecular Medicine e12921 | 2020 9 of 19 Hampel et al, 2004, 2005; Buerger et al, 2009; Glodzik-Sobanska et al, 2009; Meredith et al, 2013; Spiegel et al, 2015; Wang et al, 2016; Öhrfelt…”
Total and phosphorylated tau protein as biological markers of Alzheimer’s disease
Hampel, H., Blennow, K., Shaw, L. M., Hoessler, Y. C., Zetterberg, H., & Trojanowski, J. Q. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2009.10.010 · Cited by 389 · see citing works
“…et al., 2009) and concentration of p-tau231 declined longitudinally from mild to moderate AD (Hampel et al., 2001) and correlated significantly at baseline with rate of hippocampal atrophy in mild to moderate AD, acting as an indicator of structural disease progression (Hampel et al., 2005).”
BackgroundSelf-citationFagan, 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 · see citing works
Chronic stress and glucocorticoids: From neuronal plasticity to neurodegeneration
Vyas, S., Rodrigues, A. J., Silva, J. M., Tronche, F., Almeida, O. F. X., Sousa, N., & Sotiropoulos, I. (2016) · Neural Plasticity · doi:10.1155/2016/6391686 · Cited by 297 · see citing works
Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer’s disease
Heslegrave, A., Heywood, W., Paterson, R., Magdalinou, N., Svensson, J., Johansson, P., Öhrfelt, A., Blennow, K., Hardy, J., Schott, J., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0071-x · Cited by 303 · see citing works
“are reflected in the CSF by increased total tau (T-tau) and phospho-tau (P-tau) concentrations, respectively [15–18] whereas cerebral Aβ plaque pathology is reflected by reduced CSF levels of the 42 amino acidlong, aggregation-prone Aβ protein (Aβ42) [19, 20].”
BackgroundBiochemistry of Tau in Alzheimer’s disease and related neurological disorders
Sergeant, N., Bretteville, A., Hamdane, M., Caillet-Boudin, M.-L., Grognet, P., Bombois, S., Blum, D., Delacourte, A., Pasquier, F., Vanmechelen, E., et al. (2008) · Expert Review of Proteomics · doi:10.1586/14789450.5.2.207 · Cited by 300 · see citing works
Role of structural MRI in Alzheimer's disease
Vemuri, P., & Jack, C. R. (2010) · Alzheimer s Research & Therapy · doi:10.1186/alzrt47 · Cited by 246 · see citing works
“, 22 AD CSF p-tau231 correlated with baseline hippocampus and rates of 2005 [73] hippocampal atrophy.”
BackgroundSotiropoulos, I., Catania, C., Pinto, L., Silva, R., Pollerberg, G. E., Takashima, A., Sousa, N. J., & Almeida, O. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0730-11.2011 · Cited by 265 · see citing works
Zetterberg, H. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.90 · Cited by 234 · see citing works
“Phosphorylated tau measured in CSF samples taken during life correlate with neocortical tangle pathology at autopsy,(23) and CSF P-tau also correlates with the rate of hippocampal atrophy in the brain.(24) The CSF level of P-tau thus seems to reflect the phosphorylation state of tau and the formation of tangles in the…”
Fjell, A. M., Walhovd, K. B., Fennema‐Notestine, C., McEvoy, L. K., Hagler, D. J., Holland, D., Brewer, J. B., Dale, A. M., & Initiative, A. D. N. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3785-09.2010 · Cited by 209 · see citing works
“A relationship between CSF biomarker levels and hippocampal volume or atrophy has been shown in vivo (Hampel et al., 2005; de Leon et al., 2006; Fjell et al., 2008).”
InfluentialDiagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease
Tarawneh, R. M., D’Angelo, G., Crimmins, D. L., Herries, E. M., Griest, T. A., Fagan, A. M., Zipfel, G. J., Ladenson, J. H., Morris, J. C., & Holtzman, D. M. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.0086 · Cited by 219 · see citing works
Safiri, S., Jolfayi, A. G., Fazlollahi, A., Morsali, S., Sarkesh, A., Sorkhabi, A. D., Golabi, B., Aletaha, R., Asghari, K. M., Hamidi, S., et al. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1474043 · Cited by 242 · see citing works
Rates of cerebral atrophy differ in different degenerative pathologies
Whitwell, J. L., Jack, C. R., Parisi, J. E., Knopman, D. S., Boeve, B. F., Petersen, R. C., Ferman, T. J., Dickson, D. W., & Josephs, K. A. (2006) · Brain · doi:10.1093/brain/awm021 · Cited by 167 · see citing works
“A number of studies have demonstrated correlations between the presence of temporal lobe atrophy and the presence and severity of neurofibrillary tangles (Nagy et al., 1996; Jack et al., 2002), as well as cerebrospinal fluid levels of tau in Alzheimer's disease (Hampel et al., 2005).”
BackgroundBiological markers of amyloid β-related mechanisms in Alzheimer's disease
Hampel, H. J., Shen, Y., Walsh, D. M., Aisen, P. S. S., Shaw, L. M., Zetterberg, H., Trojanowski, J. Q., & Blennow, K. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.09.024 · Cited by 159 · see citing works
“Combination and integration of multimodal imaging, genetic and neurochemical markers is still in its infancy; however, there are early studies combining CSF and MRI markers (Hampel et al., 2005) or CSF pattern and regional cerebral blood flow for added value (Haense et al.”
BackgroundSelf-citationMRI and CSF biomarkers in normal, MCI, and AD subjects
Vemuri, P., Wiste, H. J., Weigand, S. D., Shaw, L. M. J., Trojanowski, J. Q., Weiner, M. W., Knopman, D. S., Petersen, R. C., & Jack, C. R. (2009) · Neurology · doi:10.1212/wnl.0b013e3181af79e5 · Cited by 246 · see citing works
Multicenter assessment of CSF-phosphorylated tau for the prediction of conversion of MCI
Ewers, M., Büerger, K., Teipel, S. J., Scheltens, P., Schröder, J., Zinkowski, R. P., Bouwman, F. H., Schönknecht, P., Schoonenboom, N. S. M., Andreasen, N. C., et al. (2007) · Neurology · doi:10.1212/01.wnl.0000286944.22262.ff · Cited by 142 · see citing works
Self-citationHyperphosphorylation and Cleavage at D421 Enhance Tau Secretion
Plouffe, V., Mohamed, N., Rivest‐McGraw, J., Bertrand, J., Lauzon, M., & Leclerc, N. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036873 · Cited by 146 · see citing works
“[19,20,21,22,23].”
Chiu, M., Chen, Y., Chen, T., Yang, S., Yang, F., Tseng, T.-W., Chieh, J.-J., Chen, J.-C. R., Tzen, K., Hua, M., et al. (2013) · Human Brain Mapping · doi:10.1002/hbm.22390 · Cited by 141 · see citing works
“As discussed above, the relationship between the tau level in the CSF and hippocampal atrophy has recently been studied [Desikan et al., 2011; de Souza et al., 2012; Hampel et al., 2005].”
BackgroundHampel, H. J., Lista, S., & Khachaturian, Z. S. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.05.2116 · Cited by 138 · see citing works
“[57] Hampel H, B€urger K, Pruessner JC, Zinkowski R, DeBernardis J,”
BackgroundSelf-citationCSF tau markers are correlated with hippocampal volume in Alzheimer's disease
de Souza, L. C., Marie Chupin, A., Lamari, F., Jardel, C., Leclercq, D., Olivier Colliot, A., Lehéricy, S., Dubois, B., & Sarazin, M. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.02.022 · Cited by 125 · see citing works
“Longitudinal data also showed that elevated baseline levels of CSF P-tau were associated with higher rates of hippocampal atrophy in mild cognitive impairment (MCI) (Fjell et al., 2010) and in AD patients (Hampel et al., 2005; Henneman et al., 2009).”
3D PIB and CSF biomarker associations with hippocampal atrophy in ADNI subjects
Apostolova, L. G., Hwang, K., Andrawis, J. P., Green, A. E., Babakchanian, S., Morra, J. H., Cummings, J. L., Toga, A. W., Trojanowski, J. Q., Shaw, L. M. J., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.003 · Cited by 137 · see citing works
Complement receptor 1 (CR1) and Alzheimer's disease
Crehan, H., Holton, P., Wray, S., Pocock, J., Guerreiro, R., & Hardy, J. (2012) · Immunobiology · doi:10.1016/j.imbio.2011.07.017 · Cited by 129 · see citing works
Upcoming Candidate Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease
Fagan, A. M., & Perrin, R. J. (2012) · Biomarkers in Medicine · doi:10.2217/bmm.12.42 · Cited by 115 · see citing works
Voxel-based morphometry in Alzheimer’s disease
Busatto, G. F., Diniz, B. S., & Zanetti, M. V. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.11.1691 · Cited by 144 · see citing works
Pathak, N., Vimal, S. K., Tandon, I., Agrawal, L., Cao, H., & Bhattacharyya, S. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00800-w · Cited by 149 · see citing works
Cacciaglia, R., Molinuevo, J. L., Falcón, C., Brugulat‐Serrat, A., Sánchez‐Benavides, G., Gramunt, N., Esteller, M., Morán, S., Minguillón, C., Fauria, K., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.01.016 · Cited by 124 · see citing works
“In addition, a lower hippocampal volume in nondemented individuals has been reported to increase the risk of developing AD [35,36] and to be associated to higher cerebrospinal fluid tau levels [37].”
Spatial patterns of brain amyloid- burden and atrophy rate associations in mild cognitive impairment
Tosun, D., Schuff, N. W., Mathis, C. A., Jagust, W., Weiner, M. W., & Initiative, A. D. N. (2011) · Brain · doi:10.1093/brain/awr044 · Cited by 117 · see citing works
Brain Atrophy in Healthy Aging Is Related to CSF Levels of Aβ1-42
Fjell, A. M., Walhovd, K. B., Fennema‐Notestine, C., McEvoy, L. K., Hagler, D. J., Holland, D., Blennow, K., Brewer, J. B., Dale, A. M., & Initiative, T. A. D. N. (2010) · Cerebral Cortex · doi:10.1093/cercor/bhp279 · Cited by 105 · see citing works
“…causative roles in neurodegeneration in Alzheimer’s disease (AD; Goedert and Spillantini 2006; Spires-Jones et al. 2009a), and CSF levels of these biomarkers correlate with rates of atrophy and ventricular expansion (Hampel et al. 2005; de Leon et al. 2006; Chou et al. 2009; Schuff et al. 2009).”
Propagation of Tau via Extracellular Vesicles
Pérez, M., Avila, J., & Hernández, F. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00698 · Cited by 118 · see citing works
“, 2000) or T231 (Hampel et al., 2005) has been described in the cerebrospinal fluid of AD patients, although a decrease with the progression of AD has also been reported (Hampel et al.”
BackgroundCSF and MRI markers independently contribute to the diagnosis of Alzheimer's disease
Schoonenboom, N. S. M., van der Flier, W. M., Blankenstein, M. A., Bouwman, F. H., van Kamp, G. J., Barkhof, F., & Scheltens, P. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.11.018 · Cited by 106 · see citing works
Tosun, D., Schuff, N. W., Truran‐Sacrey, D., Shaw, L. M. J., Trojanowski, J. Q., Aisen, P. S. S., Peterson, R., & Weiner, M. W. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.030 · Cited by 98 · see citing works
Sotiropoulos, I., Catania, C., Riedemann, T., Fry, J. P., Breen, K. C., Michaelidis, T. M., & Almeida, O. F. X. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05613.x · Cited by 97 · see citing works
“These sites are hyperphosphorylated in AD and the antibodies that recognize these sites constitute important diagnostic tools which are associated with the severity and progression of AD pathology (Holzer et al. 1994; Augustinack et al. 2002; Hampel et al. 2005).”
BackgroundSelnes, P., Aarsland, D., Bjørnerud, A., Gjerstad, L., Wallin, A., Hessen, E., Reinvang, I., Grambaitė, R., Auning, E., Kjærvik, V. K., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121603 · Cited by 99 · see citing works
“We also reproduce earlier findings showing that CSF biomarkers predict cognitive decline and medial temporal lobe atrophy [45, 46].”
Tarawneh, R. M., Head, D. M., Allison, S. L., Buckles, V., Fagan, A. M., Ladenson, J. H., Morris, J. C., & Holtzman, D. M. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.0202 · Cited by 96 · see citing works
Kang, J., Vanderstichele, H., Trojanowski, J. Q., & Shaw, L. M. J. (2012) · Methods · doi:10.1016/j.ymeth.2012.03.023 · Cited by 107 · see citing works
The association between tau PET and retrospective cortical thinning in clinically normal elderly
LaPoint, M. R., Chhatwal, J. P., Sepulcre, J., Johnson, K. A., Sperling, R. A., & Schultz, A. P. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.05.049 · Cited by 84 · see citing works
“They have shown a relationship between baseline CSF tau measures and rates of hippocampal atrophy in AD, MCI, and CN groups (Hampel et al., 2005; Henneman et al., 2009), and in MCI subjects, between baseline CSF tau and rates of thinning in medial and lateral temporal regions (Tosun et al., 2011).”
BackgroundMethodQin, Y., Liu, Y., Hao, W., Decker, Y., Tomic, I., Menger, M. D., Liu, C., & Fassbender, K. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600873 · Cited by 90 · see citing works
“proteins are both elevated, which have been even observed to be the predictors for the future brain atrophy during AD progression (2, 3).”
BackgroundWhite matter hyperintensities are associated with disproportionate progressive hippocampal atrophy
Fiford, C. M., Manning, E. N., Bartlett, J. W., Cash, D. M., Malone, I. B., Ridgway, G. R., Lehmann, M., Leung, K. K., Sudre, C. H., Sebastien Ourselin, A., et al. (2016) · Hippocampus · doi:10.1002/hipo.22690 · Cited by 94 · see citing works
“Hippocampal atrophy is an early marker of AD pathology (Henneman et al., 2009; Dubois et al., 2014); rates correlate with cerebrospinal fluid (CSF) markers of AD (Hampel et al., 2005; Schuff et al., 2009) and also with cognitive decline (Jack et al., 2000).”
Chronic Sleep Disruption Advances the Temporal Progression of Tauopathy in P301S Mutant Mice
Zhu, Y., Zhan, G., Fenik, P., Brandes, M., Bell, P., François, N., Shulman, K., & Veasey, S. C. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0275-18.2018 · Cited by 106 · see citing works
“In AD, increased P231 tau levels in the CSF predict lower hippocampal volumes and greater declines in volume over time (Hampel et al., 2005), and P231 tau levels predict cognitive decline in individuals with mild cognitive impairment (Buerger et al., 2002).”
BackgroundReduced sample sizes for atrophy outcomes in Alzheimer's disease trials: baseline adjustment
Schott, J., Bartlett, J., Barnes, J., Leung, K. K., Ourselin, S., & Fox, N. C. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.011 · Cited by 84 · see citing works
“Several studies found increased hippocampal rates to be associated with higher levels of p-tau in MCI (de Leon et al., 2006; Hampel et al., 2005; Henneman et al., 2009), while in established AD, a weak association between baseline p-tau and whole brain atrophy has been reported (Sluimer et al.,…”
Frölich, L., Peters, O., Lewczuk, P., Gruber, O., Teipel, S. J., Gertz, H., Jahn, H., Jessen, F., Kurz, A., Luckhaus, C., et al. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0301-7 · Cited by 75 · see citing works
“A wealth of data exists to show that the brain changes on MRI are related to CSF biomarkers, but also reveal complementary information [11, 21, 22].”
BackgroundSelf-citationHenneman, W. J. P., Vrenken, H., Barnes, J., Sluimer, I. C., Verwey, N. A., Blankenstein, M. A., Klein, M., Fox, N. C., Scheltens, P., Barkhof, F., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b879ac · Cited by 75 · see citing works
“p-Tau 63 (35) 87 (30)* 92 (38)* 83 (36)”
Thambisetty, M., Hye, A., Foy, C., Daly, E., Glover, A., Cooper, A., Simmons, A., Murphy, D., & Lovestone, S. (2008) · Journal of Neurology · doi:10.1007/s00415-008-0006-8 · Cited by 80 · see citing works
“increased total and p-tau in CSF are considered to be among the most robust biomarkers for AD and MCI [6, 7, 8] both these proteins are positively correlated with baseline hippocampal volume [17].”
BackgroundResultGuzman, V. A., Carmichael, O. T., Schwarz, C. G., Tosto, G., Zimmerman, M. E., Brickman, A. M., & Initiative, A. D. N. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.11.009 · Cited by 74 · see citing works
“Although atrophic changes are thought to be most related to tau pathology (1), findings have been somewhat inconsistent in the literature, with some groups showing an association between tau and brain atrophy (34– 37) and others showing no or modest associations in non-demented samples (38, 39).”
Shekhar, S., Kumar, R. K., Rai, N., Kumar, V. L., Singh, K. K., Upadhyay, A. D., Tripathi, M., Dwivedi, S. N., Dey, A. B., & Dey, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0159099 · Cited by 80 · see citing works
“It has also been reported that increased phosphorylation at p-Tau181 has correlation with hippocampal atrophy [21].”
BackgroundWhole-brain atrophy rate and CSF biomarker levels in MCI and AD: a longitudinal study
Sluimer, J. D., Bouwman, F. H., Vrenken, H., Blankenstein, M. A., Barkhof, F., van der Flier, W. M., & Scheltens, P. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.06.016 · Cited by 106 · see citing works
Ossenkoppele, R., Mattsson, N., Teunissen, C. E., Barkhof, F., Pijnenburg, Y. A. L., Scheltens, P., van der Flier, W. M., & Rabinovici, G. D. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.011 · Cited by 71 · see citing works
Amyloid β (Aβ) and phospho-tau (p-tau) as diagnostic biomarkers in Alzheimer's disease
Prvulovic, D., & Hampel, H. J. (2011) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.087 · Cited by 73 · see citing works
“In mild to moderate AD, CSF p-tau231 concentrations at baseline predicted the rate of subsequent hippocampal atrophy (112).”
Self-citationBiochemical Markers in Alzheimer’s Disease
Rabbito, A., Dulewicz, M., Kulczyńska‐Przybik, A., & Mroczko, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21061989 · Cited by 105 · see citing works
“Instead, CSF levels of phosphorylated tau seem to reflect the formation of neurofibrillary tangles in the brain [51,52].”
BackgroundGerson, J. E., Castillo‐Carranza, D. L., & Kayed, R. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500143n · Cited by 73 · see citing works
Biomarkers in Alzheimer's disease drug development
Cummings, J. L. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.06.004 · Cited by 121 · see citing works
“correlated with hippocampal atrophy at baseline and with rates of hippocampal atrophy in patients with AD [79].”
BackgroundGispert, J. D., Rami, L., Sánchez‐Benavides, G., Falcón, C., Tucholka, A., Rojas, S., & Molinuevo, J. L. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.06.027 · Cited by 56 · see citing works
Meisenzahl, E. M., Seifert, D., Ronald Bottlender, A., Teipel, S. J., Zetzsche, T., Jäger, M., Koutsouleris, N., Schmitt, G., Scheuerecker, J., Burgermeister, B., et al. (2009) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-009-0023-3 · Cited by 56 · see citing works
“It should be noted that beside schizophrenia and MD hippocampal shrinkage is observed in a large range of other neuropsychiatric diseases such as AD and personality disorders [21, 22, 50, 59].”
BackgroundSelf-citationFjell, A. M., Walhovd, K. B., Amlien, I. K., Bjørnerud, A., Reinvang, I., Gjerstad, L., Cappelen, T., Willoch, F., Due‐Tønnessen, P., Grambaitė, R., et al. (2008) · American Journal of Neuroradiology · doi:10.3174/ajnr.a1059 · Cited by 60 · see citing works
Paterson, R. W., Toombs, J., Slattery, C. F., Nicholas, J. M., Andréasson, U., Magdalinou, N. K., Blennow, K., Warren, J. D., Mummery, C. J., Rossor, M. N., et al. (2015) · Journal of Neurology · doi:10.1007/s00415-015-7904-3 · Cited by 56 · see citing works
“Ab1-42 is inversely correlated with amyloid load [15, 16]; T-tau is thought to reflect the intensity of neurodegeneration [17], and P-tau correlates with neurofibrillary tangle burden [18, 19].”
Li, X., Li, T., Andreasen, N. C., Wiberg, M. K., Westman, E., & Wahlund, L. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12164 · Cited by 55 · see citing works
Initiative, A. D. N., Stricker, N. H., Dodge, H. H., Dowling, N. M., Han, S. D., Erosheva, E. A., & Jagust, W. (2012) · Brain Imaging and Behavior · doi:10.1007/s11682-012-9171-6 · Cited by 53 · see citing works
“Other studies have demonstrated a significant relationship between p-tau231p or p-tau181p and accelerated hippocampal atrophy in MCI (de Leon et al. 2006; Fjell et al. 2010; Hampel et al. 2005; Tosun et al. 2010).”
InfluentialCerebrospinal fluid and blood biomarkers in Alzheimer’s disease
Humpel, C. (2011) · World Journal of Psychiatry · doi:10.5498/wjp.v1.i1.8 · Cited by 51 · see citing works
Tau acts as a mediator for<scp>A</scp>lzheimer's disease‐related synaptic deficits
Liao, D., Miller, E. C., & Teravskis, P. J. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12504 · Cited by 53 · see citing works
“The presence of hyperphosphorylated tau in human cerebrospinal fluid has been shown to predict future AD in patients with mild cognitive impairment (Buerger et al., 2005; Hampel et al., 2005; Hansson et al., 2006).”
BackgroundThomann, P., Kaiser, E., Schönknecht, P., Pantel, J., Essig, M., & Schröder, J. (2009) · Journal of Psychiatry & Neuroscience · doi:10.1139/jpn.0918 · Cited by 53 · see citing works
The development of effective biomarkers for Alzheimer's disease: a review
Henry, M. S., Passmore, A. P., Todd, S., McGuinness, B., Craig, D., & Johnston, J. A. (2012) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.3829 · Cited by 49 · see citing works
“MCI studies have correlated high initial CSF P-tau231 concentrations with subsequent cognitive decline and progression to AD, along with structural disease progression measured by hippocampal atrophy (Buerger et al., 2002a; Hampel et al., 2005).”
BackgroundTosun, D., Initiative1, T. A. D. N., Schuff, N. W., Shaw, L. M. J., Trojanowski, J. Q., & Weiner, M. W. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-0006 · Cited by 52 · see citing works
“Our findings in this study are largely consistent with several similar studies on relationships between CSF biomarkers and brain alterations in MCI and AD [40–42].”
InfluentialMenopause hormone therapy significantly alters pathophysiological biomarkers of Alzheimer's disease
Depypere, H. T., Vergallo, A., Lemercier, P., Lista, S., Benedet, A. L., Ashton, N. J., Cavedo, E., Zetterberg, H., Blennow, K., Vanmechelen, E., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12759 · Cited by 60 · see citing works
“…(p-tau 231 ), a particularly early indicator of AD related tau protein phosphorylation and neurofibrillary pathology, 32 rate of hippocampal atrophy 33 and rate of regional brain atrophy, longitudinal patterns of brain networks functional decline, and indirectly reflects A β plaque rates of…”
BackgroundSelf-citationChen, J., Fears, S. C., Jasinska, A. J., Huang, A., Al‐Sharif, N., Scheibel, K. E., Dyer, T. D., Fagan, A. M., Blangero, J., Woods, R. P., et al. (2018) · Brain and Behavior · doi:10.1002/brb3.903 · Cited by 50 · see citing works
“Previous work has demonstrated associations between longitudinal changes in Aβ1–42 and ptau231 and hippocampal volume in AD and mild cognitive impairment (Chou et al., 2009; De Leon et al., 2006; Hampel et al., 2005; Schuff et al., 2009) as well as in healthy brain aging (Fjell et al.”
BackgroundVisual ratings of atrophy in MCI: prediction of conversion and relationship with CSF biomarkers
Lehmann, M., Koedam, E., Barnes, J., Bartlett, J. W., Barkhof, F., Wattjes, M. P., Schott, J. M., Scheltens, P., & Fox, N. C. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.03.010 · Cited by 46 · see citing works
“Some studies have also reported associations of tau and p-tau levels with hippocampal volumes in MCI (Fjell et al., 2008) and AD (Hampel et al., 2005), however, others have not found such a relationship (Schuff et al., 2009).”
Gunnarsson, M. D., Lannfelt, L., Ingelsson, M., Basun, H., & Kilander, L. (2013) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000355556 · Cited by 56 · see citing works
CSF Aβ42, Tau and Phosphorylated Tau Correlate with Medial Temporal Lobe Atrophy
Herukka, S.-K., Pennanen, C., Soininen, H., & Pirttilä, T. (2008) · Journal of Alzheimer's Disease · doi:10.3233/jad-2008-14105 · Cited by 47 · see citing works
“One study reported a positive correlation between CSF tau and phospho-tau231 and hippocampal volume at baseline in 22 AD patients with mild dementia [10] whereas no correlation was found in a larger study involving 88 AD patients [22].”
Deák, F., Freeman, W. M., Ungvari, Z. I., Csiszár, A., & Sonntag, W. E. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glv206 · Cited by 44 · see citing works
Chronic pain causes Tau-mediated hippocampal pathology and memory deficits
Guerreiro, S. R., Guimarães, M. R., Silva, J., Dioli, C., Vamvaka-Iakovou, A., Sousa, R., Gomes, P. A., Megalokonomou, A., Campos-Marques, C., Cunha, A. M., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01707-3 · Cited by 44 · see citing works
“Phosphorylation at Thr231 epitope is suggested to reduce Tau binding capacity to microtubules [35] while it is correlated with hippocampal atrophy in AD patients [36].”
BackgroundTau as the Converging Protein between Chronic Stress and Alzheimer's Disease Synaptic Pathology
Sotiropoulos, I., & Sousa, N. (2015) · Neurodegenerative Diseases · doi:10.1159/000440844 · Cited by 40 · see citing works
Plasma Tau Levels in Cognitively Normal Middle-Aged and Older Adults
Chiu, M., Fan, L., Chen, T., Chen, Y., Chieh, J.-J., & Horng, H. E. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00051 · Cited by 48 · see citing works
Gupta, V. B., Doecke, J. D., Hone, E., Pedrini, S., Laws, S. M., Thambisetty, M., Bush, A. I., Rowe, C. C., Villemagne, V. L., Ames, D. J., et al. (2015) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2015.12.001 · Cited by 40 · see citing works
“Hippocampal atrophy is known to happen in the early stages of the disease, during the conversion from MCI to AD, and even considered as a marker in the late stages of AD [20,21].”
BackgroundNeuroimaging predictors of brain amyloidosis in mild cognitive impairment
Tosun, D., Joshi, S. C., & Weiner, M. W. (2013) · Annals of Neurology · doi:10.1002/ana.23921 · Cited by 42 · see citing works
Early risk assessment for Alzheimer's disease
Carrillo, M. C., Blackwell, A. D., Hampel, H. J., Lindborg, J., Sperling, R. A., Schenk, D., Sevigny, J., Ferris, S. H., Bennett, D. A., Craft, S., et al. (2009) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2009.01.019 · Cited by 42 · see citing works
“As people age, the hippocampal volume decreases [97], regardless of whether the person becomes demented or not.”
BackgroundSelf-citationBiological markers for early detection and pharmacological treatment of Alzheimer's disease
Hampel, H. J., Broich, K., Hoessler, Y. C., & Pantel, J. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.2/hhampel · Cited by 50 · see citing works
Self-citationMaurin, H., Chong, S., Kraev, I., Davies, H. A., Kremer, A., Seymour, C. M., Lechat, B., Jaworski, T., Borghgraef, P., Devijver, H., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087605 · Cited by 42 · see citing works
Qin, Y., Zhang, Y., Tomic, I., Hao, W., Menger, M. D., Liu, C., Fassbender, K. C., & Liu, Y. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180426 · Cited by 47 · see citing works
Kiđemet‐Piskač, S., Leko, M. B., Blažeković, A., Horvat, L. L., Klepac, N., Sonicki, Z., Kolenc, D., Hof, P. R., Boban, M., Mimica, N., et al. (2018) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12814 · Cited by 37 · see citing works
Cerebrospinal Fluid Biomarkers of Alzheimer's Disease
Fagan, A. M., & Holtzman, D. M. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.09.83 · Cited by 85 · see citing works
Alzheimer disease seen through the lens of sex and gender
Castro‐Aldrete, L., Einsiedler, M., Martínková, J., Depypere, H. T., Ang, T. F. A., Mielke, M. M., Sindi, S., Eyre, H. A., Au, R., Dimech, A. S., et al. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-025-01071-0 · Cited by 39 · see citing works
“Similarly, p-tau 231 is under investigation as a CSF biomarker of prodromal AD 257–259 .”
Frank, B. E., Ally, M., Brekke, B., Zetterberg, H., Blennow, K., Sugarman, M. A., Ashton, N. J., Karikari, T. K., Tripodis, Y., Martin, B. M., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12508 · Cited by 40 · see citing works
T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease
Haris, M., Yadav, S. K., Rizwan, A., Singh, A., Cai, K., Kaura, D., Wang, E., Davatzikos, C., Trojanowski, J. Q., Melhem, E. R., et al. (2015) · NeuroImage: Clinical · doi:10.1016/j.nicl.2015.02.016 · Cited by 33 · see citing works
“The same study has also reported, no significant effect of T-tau level on hippocampal atrophy (Hampel et al., 2005).”
BackgroundStress and the Etiopathogenesis of Alzheimer’s Disease and Depression
Sotiropoulos, I., Silva, J. M., Gomes, P., Sousa, N., & Almeida, O. F. X. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9358-8_20 · Cited by 42 · see citing works
Amalric, M., Pattij, T., Sotiropoulos, I., Silva, J. M., Sousa, N., Ztaou, S., Chiamulera, C., Wahlberg, L. U., Emerich, D. F., & Paolone, G. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.661973 · Cited by 35 · see citing works
Fjell, A. M., Amlien, I. K., Westlye, L. T., Stenset, V. T. V., Fladby, T., Skinningsrud, A., Eilsertsen, D. E., Bjørnerud, A., & Walhovd, K. B. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.09.029 · Cited by 32 · see citing works
“Previous studies have shown correlations between hippocampal atrophy and CSF biomarker levels (de Leon et al., 2006; Hampel et al., 2005; Schuff et al., 2009; Sluimer et al., in press), but few studies have looked at the effects outside the temporal lobe.”
Zimmer, E. R., Leuzy, A., Bhat, V., Gauthier, S., & Rosa-Neto, P. (2014) · Translational Neurodegeneration · doi:10.1186/2047-9158-3-6 · Cited by 30 · see citing works
“Additionally, several studies have shown the degree of tau pathology to correlate with synaptic dysfunction and brain atrophy, as well as the severity of cognitive decline [11-13].”
BackgroundAmro, Z., Yool, A. J., & Collins‐Praino, L. E. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100242 · Cited by 37 · see citing works
Wang, L., Fagan, A. M., Shah, A. R., Beg, M. F., Csernansky, J. G., Morris, J. C., & Holtzman, D. M. (2011) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31823c0cf4 · Cited by 32 · see citing works
Zeng, P. H., Su, H.-F., Ye, C., Qiu, S.-W., Shi, A., Wang, J., Zhou, X., & Tian, Q. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.877806 · Cited by 32 · see citing works
- Authors
- Hampel, H., Bürger, K., Pruessner, J. C., Zinkowski, R., DeBernardis, J., Kerkman, D., Leinsinger, G., Evans, A. C., Davies, P., Möller, H.-J., & Teipel, S. J.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2005-05-01
- Volume
- 62
- Issue
- 5
- Pages
- 770
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2032332012
- Cited by
- 175
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 10 · 2013: 10 · 2012: 10
- FWCI
- 6.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- 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
- tau phosphorylation, cerebrospinal fluid biomarkers, hippocampal atrophy, hippocampal volume, Alzheimer's disease, disease progression, neuronal loss, magnetic resonance imaging
- MeSH terms
- Aged, Alzheimer Disease, Atrophy, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Phosphorylation, Statistics as Topic, Threonine, tau Proteins
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