CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies
Abstract
Tau and beta-amyloid (1-42) (Abeta42) are two independent markers for the early diagnosis of Alzheimer's disease (AD). In the present study, biochemical markers were validated as tools for differential diagnosis between AD and dementia with Lewy bodies (DLB). Tau, Abeta42 and phospho-tau (181P) were measured in cerebrospinal fluid (CSF) from controls (n=40) and from patients with AD (n=80) or DLB (n=43) using the HT7-AT270 assay (prototype version). In comparison with AD, in DLB no differences were found for Abeta42 and lower phospho-tau. ROC analysis was used to compare the discriminatory power of total tau with that of phospho-tau. The area under the curve (AUC) amounted to 0.782 +/- 0.048 (mean +/- SE) for tau and to 0.839 +/- 0.042 for phospho-tau (p = 0.039) for differentiation of AD from DLB. The present results indicate that CSF phospho-tau may be a good marker for differentiation between AD and DLB.
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P-tau's level is consistently elevated in AD when compared with frontotemporal dementia, Lewy body dementia, and control.
“It has also been shown that the P-tau's level consistently elevated in AD when compared with frontotemporal dementia (FTD), lewy body dementia (LBD), and control (Parnetti et al., 2001).”
From T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease (2015) · cites this paper as Parnetti et al., 2001
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“For example, at a sensitivity level of 81%, CSF t-tau protein achieved only a 57% specificity to distinguish AD from other dementias (Hulstaert et al., 1999; Parnetti et al., 2001).”
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“Also p-t has been suggested to be a marker for distinguishing AD from DLB (Parnetti et al., 2001; Vanderstichele et al., 2006).”
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“…in agreement with results published previously which further confirm the important role of phosphorylated species of tau proteins in the diagnosis of AD (Parnetti et al., 2001; Sjögren et al., 2001; Sjögren et al., 2002; Hampel et al., 2004; Maddalena et al., 2003; Riemenschneider et al., 2003).”
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“Some studies also suggest that the concentration of phosphorylated tau in CSF, which is highly correlated with total tau levels, may provide a higher specificity to differentiate AD and DLB (Parnetti et al., 2001; Vanderstichele et al., 2006).”
BackgroundCSF tau and β-amyloid as biomarkers for mild cognitive impairment
Hampel, H., & Blennow, K. (2004) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2004.6.4/hhampel · Cited by 52 · see citing works
“Results showed a significant increase in CSF P-tau181 concentrations in AD compared with FTD and controls.22 Focusing on the differentiation between AD and LBD, specificity at a given sensitivity level was improved by using P-tau181 compared with T-tau.45,95 Comparing receiver operator characteristic (ROC) curves led…”
InfluentialAmyloid-beta and tau proteins as biochemical markers of Alzheimer's disease
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“CSF P-MAP-tau has been reported to be normal (concentrations similar to control groups) in DLB (Buerger et al. 2002b, Itoh et al. 2001, Parnetti et al. 2001), FTD (Buerger et al. 2002b, Rosso et al. 2003) or VaD (Buerger et al. 2002b, Hu et al. 2002, Itoh et al. 2001, Nagga et al. 2002, Schonknecht…”
BackgroundClinical significance of fluid biomarkers in Alzheimer’s Disease
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“differentiating between AD and DLB [10].”
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“Previous studies demonstrated, that above a certain threshold concentrationMCI patients turn out to show the Alzheimer symptomswith a probability of up to 80% (Parnetti et al., 2001).”
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“These CSF biomarkers reflect the main neuropathological features of AD, but the ability of these markers to distinguish AD from DLB is limited (Parnetti et al., 2001; Mollenhauer et al., 2005).”
BackgroundCSF biomarkers in neurodegenerative and vascular dementias
Llorens, F., Schmitz, M., Ferrer, I., & Zerr, I. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.03.003 · Cited by 39 · see citing works
“Elevated P-tau levels are relevant in AD diagnosis as they permit discrimination between AD and FTLD-TDP-43, PDD, DLB and VaD (Hampel et al., 2004; Kaerst et al., 2013a; Kohnken et al., 2000; Parnetti et al., 2001; Sjogren et al., 2001; Vanmechelen et al., 2000).”
BackgroundBiomarkers in biological fluids for dementia with Lewy bodies
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“Since the phosphorylation of tau protein in brain occurs to a lesser extent in DLB [51,52], the quantification of phosphorylated tau species in CSF may serve as a specific marker to discriminate AD from DLB [50,53].”
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“In particular P-tau-231 (tau protein phosphorylated at the threonine 231) has proven useful in differentiating AD from FTD, DLB, VaD, and normal controls.(24,71,78,79) P-tau-231 also distinguishes AD from major depression.”
BackgroundCSF Tau, Aβ42, and MHPG Differentiate Dementia with Lewy Bodies from Alzheimer's Disease
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“shown that the P-tau3s level consistently elevated in AD when compared with frontotemporal dementia (FTD), lewy body dementia (LBD), and control (Parnetti et al., 2001).”
BackgroundNeurochemical dementia diagnostics in Alzheimer’s disease: where are we now and where are we going?
Lewczuk, P., & Kornhuber, J. (2011) · Expert Review of Proteomics · doi:10.1586/epr.11.37 · Cited by 28 · see citing works
Amyloid-specific T-cells differentiate Alzheimer's disease from Lewy body dementia.
Lanuti, P., Ciccocioppo, F., Bonanni, L., Marchisio, M., Lachmann, R., Tabet, N., Pierdomenico, L., Santavenere, E., Catinella, V., Iacone, A., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.01.004 · Cited by 30 · see citing works
Biomarkers for Alzheimer Disease in Cerebrospinal Fluid, Urine, and Blood
Lönneborg, A. (2008) · Molecular Diagnosis & Therapy · doi:10.1007/bf03256296 · Cited by 33 · see citing works
de Bont, J. D., Vanderstichele, H., Reddingius, R., Pieters, R., & van Gool, S. (2008) · European journal of paediatric neurology · doi:10.1016/j.ejpn.2007.09.007 · Cited by 28
Post Traumatic Stress Disorder Heralding the Onset of Semantic Frontotemporal Dementia
Bonanni, L., Franciotti, R., Martinotti, G., Vellante, F., Flacco, M., Giannantonio, M. D., Thomas, A., & Onofrj, M. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-171134 · Cited by 27 · see citing works
Secondary neurodegeneration following Stroke: what can blood biomarkers tell us?
Brunelli, S., Giannella, E., Bizzaglia, M., Angelis, D. D., & Sancesario, G. M. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1198216 · Cited by 30 · see citing works
Lachno, D., Romeo, M. J., Siemers, E., Vanderstichele, H., Coart, E., Konrad, R. J., Zajac, J. J., Talbot, J., Jensen, H. F., Sethuraman, G., et al. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110296 · Cited by 26 · see citing works
The role of biologic markers in the diagnosis of Alzheimer's disease
Schipper, H. (2007) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2007.07.015 · Cited by 26 · see citing works
Gmitterová, K., Gawinecka, J., Llorens, F., Varges, D., Valkovič, P., & Zerr, I. (2018) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-018-0928-9 · Cited by 26 · see citing works
Neurochemical biomarkers in Alzheimer’s disease and related disorders
Bibl, M., Esselmann, H., & Wiltfang, J. (2012) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285612455367 · Cited by 20 · see citing works
“With regard to ptau, 340 http://tan.sagepub.com considerably lower concentrations than in AD have been reported for FTD, DLB and VAD, which enables a more accurate test [Hampel et al. 2004; Sjögren et al. 2001; Parnetti et al. 2001; Galasko and Marder, 2002].”
Petersen, R. C. (2007) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/01.con.0000267234.69379.4e · Cited by 29 · see citing works
Klafki, H., Lewczuk, P., Kamrowski-Kruck, H., Maler, J., Müller, K., Peters, O., Heuser, I., Jessen, F., Popp, J., Frölich, L., et al. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-1167 · Cited by 23 · see citing works
“An early event in the development of the neurofibrillary changes in AD is the abnormal hyperphosphorylation of tau protein [8–10], and elevated concentrations of phosphorylated tau (phospho-tau) in the CSF of AD patients have been reported [11–15].”
The Alzheimer Variant of Lewy Body Disease: A Pathologically Confirmed Case-Control Study
Perneczky, R., Mosch, D., Neumann, M., Kretzschmar, H., Müller, U., Busch, R., Förstl, H., & Kurz, A. (2005) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000086472 · Cited by 23 · see citing works
How many biomarkers to discriminate neurodegenerative dementia?
Sancesario, G. M., & Bernardini, S. (2015) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2015.1051658 · Cited by 22 · see citing works
Diagnostic value of cerebro-spinal fluid biomarkers in dementia with lewy bodies
Bousiges, O., & Blanc, F. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.11.027 · Cited by 17 · see citing works
The role of α-synuclein in neurodegeneration — An update
Jellinger, K. A. (2012) · Translational Neuroscience · doi:10.2478/s13380-012-0013-1 · Cited by 19 · see citing works
Disease Modifying Trials in Alzheimer's Disease: Perspectives for the Future
Vellas, B. J., Coley, N., & Andrieu, S. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15212 · Cited by 15 · see citing works
“Sensitivity and specificity levels of around 85% have been reported, and it also seems that these markers could discriminate between different types of dementia [44].”
From protein biomarkers to proteomics in dementia with Lewy Bodies
Tsamourgelis, A., Swann, P., Chouliaras, L., & O'Brien, J. T. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101771 · Cited by 18 · see citing works
Emerging Biomarkers in Cognition
Wicklund, M. R., & Petersen, R. C. (2013) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2013.07.006 · Cited by 17 · see citing works
Article Commentary: Alzheimer's Disease, Diagnosis and the Need for Biomarkers
Hooper, C., Lovestone, S., & Sáinz‐Fuertes, R. (2008) · Biomarker Insights · doi:10.4137/bmi.s682 · Cited by 14 · see citing works
“Elevated levels of phosphorylated-tau are also apparent in AD and in contrast to total tau this marker of disease seems to be more specifi c to AD as opposed to other dementias (Vanmechelen et al. 2000; Itoh et al. 2001; Parnetti et al. 2001; Nagga et al. 2002).”
Caso, F., Agosta, F., Scamarcia, P. G., Basaia, S., Canu, E., Magnani, G., Volontè, M., & Filippi, M. (2021) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2021.09.025 · Cited by 14 · see citing works
Campese, N., Palermo, G., Gamba, C. D., Beatino, M. F., Galgani, A., Belli, E., Prete, E. D., Vecchia, A. D., Vergallo, A., Siciliano, G., et al. (2021) · Expert Review of Proteomics · doi:10.1080/14789450.2021.1886929 · Cited by 23 · 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
Biological Markers and Alzheimer Disease: A Canadian Perspective
Schipper, H. M. (2010) · International Journal of Alzheimer s Disease · doi:10.4061/2010/978182 · Cited by 8 · see citing works
Zhu, Y., Wang, F., Xia, Y., Wang, L., Lin, H., Zhong, T., & Wang, X. (2024) · Reviews in the Neurosciences · doi:10.1515/revneuro-2024-0043 · Cited by 15 · see citing works
Neurochemical dementia diagnostics: assays in CSF and blood
Lewczuk, P., Hornegger, J., Zimmermann, R., Otto, M., Wiltfang, J., & Kornhuber, J. (2008) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-008-5005-3 · Cited by 11
“Recently, we investigated the Ab peptides pattern in the CSF of patients with AD, DLB, and PDD, and we observed that the ratio of the differentially altered Ab1-42 to the Ab1-37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD [3].”
BackgroundInfluentialCerebrospinal Fluid, Imaging, and Physiological Biomarkers in Dementia With Lewy Bodies
Mavroudis, I. A., Petridis, F. E., & Kazis, D. (2019) · American Journal of Alzheimers Disease & Other Dementias · doi:10.1177/1533317519869700 · Cited by 10 · see citing works
- Authors
- Parnetti, L., Lanari, A., Amici, S., Gallai, V., Vanmechelen, E., & Hulstaert, F.
- Affiliations
- University of Perugia (IT)
- Fujirebio (Belgium) (BE)
- Venue
- Neurological Sciences
- Published
- 2001-02-01
- Volume
- 22
- Issue
- 1
- Pages
- 77-78
- ISSN
- 1590-1874 (ISSN-L)
- 1590-3478
- OpenAlex
- W1987397445
- Cited by
- 141
- References
- 0
- Citations by year
- 2024: 3 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 8 · 2012: 7
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurological Sciences (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
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, dementia with Lewy bodies, cerebrospinal fluid, phosphorylated tau, tau protein, amyloid-beta 42, biomarkers, differential diagnosis, receiver operating characteristic
- MeSH terms
- Alzheimer Disease, Brain, Humans, Immunoassay, Phosphorylation, Statistics as Topic, tau Proteins, Lewy Body Disease
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