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Erschienen in: Journal of Neural Transmission 9/2009

01.09.2009 | Dementias - Original Article

Neurochemical dementia diagnostics: a simple algorithm for interpretation of the CSF biomarkers

verfasst von: Piotr Lewczuk, Rüdiger Zimmermann, Jens Wiltfang, Johannes Kornhuber

Erschienen in: Journal of Neural Transmission | Ausgabe 9/2009

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Abstract

Cerebrospinal fluid (CSF)-based neurochemical dementia diagnostics (NDD) is a well-established diagnostic tool for neurodegenerative disorders, including Alzheimer’s disease (AD). However, the direct comparison of the concentrations of the biomarkers between laboratories is often very misleading, due to relatively high inter-laboratory discrepancies of normal/abnormal ranges (cutoff values). Therefore, an interpretation tool might be useful for centers performing NDD to facilitate a standardized, diagnostic-oriented reporting of the data on biomarkers. In this study, we present a simple, easy-to-implement algorithm allowing diagnostic-relevant categorization of patients according to the outcome of the CSF NDD results and, correspondingly, enabling reporting of the data to clinicians in a clear and easy-to-follow form. The algorithm is flexible and cutoff values independent, meaning each laboratory can easily supplement it with the cutoff values and normal/abnormal ranges according to the needs; the only prerequisite is to perform the standard CSF NDD assays (amyloid β peptides and Tau/pTau).
Literatur
Zurück zum Zitat Arai H, Terajima M, Miura M, Higuchi S, Muramatsu T, Machida N, Seiki H, Takase S, Clark CM, Lee VM et al (1995) Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer’s disease. Ann Neurol 38:649–652PubMedCrossRef Arai H, Terajima M, Miura M, Higuchi S, Muramatsu T, Machida N, Seiki H, Takase S, Clark CM, Lee VM et al (1995) Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer’s disease. Ann Neurol 38:649–652PubMedCrossRef
Zurück zum Zitat Blomberg M, Jensen M, Basun H, Lannfelt L, Wahlund LO (1996) Increasing cerebrospinal fluid tau levels in a subgroup of Alzheimer patients with apolipoprotein E allele epsilon 4 during 14 months followup. Neurosci Lett 214:163–166PubMedCrossRef Blomberg M, Jensen M, Basun H, Lannfelt L, Wahlund LO (1996) Increasing cerebrospinal fluid tau levels in a subgroup of Alzheimer patients with apolipoprotein E allele epsilon 4 during 14 months followup. Neurosci Lett 214:163–166PubMedCrossRef
Zurück zum Zitat Buerger K, Otto M, Teipel SJ, Zinkowski R, Blennow K, DeBernardis J, Kerkman D, Schroder J, Schonknecht P, Cepek L, McCulloch C, Moller HJ, Wiltfang J, Kretzschmar H, Hampel H (2006) Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt-Jakob disease. Neurobiol Aging 27:10–15PubMedCrossRef Buerger K, Otto M, Teipel SJ, Zinkowski R, Blennow K, DeBernardis J, Kerkman D, Schroder J, Schonknecht P, Cepek L, McCulloch C, Moller HJ, Wiltfang J, Kretzschmar H, Hampel H (2006) Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt-Jakob disease. Neurobiol Aging 27:10–15PubMedCrossRef
Zurück zum Zitat Golombowski S, Muller-Spahn F, Romig H, Mendla K, Hock C (1997) Dependence of cerebrospinal fluid tau protein levels on apolipoprotein E4 allele frequency in patients with Alzheimer’s disease. Neurosci Lett 225:213–215PubMedCrossRef Golombowski S, Muller-Spahn F, Romig H, Mendla K, Hock C (1997) Dependence of cerebrospinal fluid tau protein levels on apolipoprotein E4 allele frequency in patients with Alzheimer’s disease. Neurosci Lett 225:213–215PubMedCrossRef
Zurück zum Zitat Graff-Radford NR, Crook JE, Lucas J, Boeve BF, Knopman DS, Ivnik RJ, Smith GE, Younkin LH, Petersen RC, Younkin SG (2007) Association of low plasma abeta42/abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol 64:354–362PubMedCrossRef Graff-Radford NR, Crook JE, Lucas J, Boeve BF, Knopman DS, Ivnik RJ, Smith GE, Younkin LH, Petersen RC, Younkin SG (2007) Association of low plasma abeta42/abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol 64:354–362PubMedCrossRef
Zurück zum Zitat Hansson O, Zetterberg H, Vanmechelen E, Vanderstichele H, Andreasson U, Londos E, Wallin A, Minthon L, Blennow K (2008) Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment. Neurobiol Aging Hansson O, Zetterberg H, Vanmechelen E, Vanderstichele H, Andreasson U, Londos E, Wallin A, Minthon L, Blennow K (2008) Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment. Neurobiol Aging
Zurück zum Zitat Itoh N, Arai H, Urakami K, Ishiguro K, Ohno H, Hampel H, Buerger K, Wiltfang J, Otto M, Kretzschmar H, Moeller HJ, Imagawa M, Kohno H, Nakashima K, Kuzuhara S, Sasaki H, Imahori K (2001) Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer’s disease. Ann Neurol 50:150–156PubMedCrossRef Itoh N, Arai H, Urakami K, Ishiguro K, Ohno H, Hampel H, Buerger K, Wiltfang J, Otto M, Kretzschmar H, Moeller HJ, Imagawa M, Kohno H, Nakashima K, Kuzuhara S, Sasaki H, Imahori K (2001) Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer’s disease. Ann Neurol 50:150–156PubMedCrossRef
Zurück zum Zitat Lewczuk P, Esselmann H, Bibl M, Beck G, Maler JM, Otto M, Kornhuber J, Wiltfang J (2004a) Tau protein phosphorylated at threonine 181 in CSF as a neurochemical biomarker in Alzheimer’s disease: original data and review of the literature. J Mol Neurosci 23:115–122PubMedCrossRef Lewczuk P, Esselmann H, Bibl M, Beck G, Maler JM, Otto M, Kornhuber J, Wiltfang J (2004a) Tau protein phosphorylated at threonine 181 in CSF as a neurochemical biomarker in Alzheimer’s disease: original data and review of the literature. J Mol Neurosci 23:115–122PubMedCrossRef
Zurück zum Zitat Lewczuk P, Esselmann H, Otto M, Maler JM, Henkel AW, Henkel MK, Eikenberg O, Antz C, Krause WR, Reulbach U, Kornhuber J, Wiltfang J (2004b) Neurochemical diagnosis of Alzheimer’s dementia by CSF Aβ42, Aβ42/Aβ40 ratio and total tau. Neurobiol Aging 25:273–281PubMedCrossRef Lewczuk P, Esselmann H, Otto M, Maler JM, Henkel AW, Henkel MK, Eikenberg O, Antz C, Krause WR, Reulbach U, Kornhuber J, Wiltfang J (2004b) Neurochemical diagnosis of Alzheimer’s dementia by CSF Aβ42, Aβ42/Aβ40 ratio and total tau. Neurobiol Aging 25:273–281PubMedCrossRef
Zurück zum Zitat Lewczuk P, Beck G, Ganslandt O, Esselmann H, Deisenhammer F, Regeniter A, Petereit HF, Tumani H, Gerritzen A, Oschmann P, Schroder J, Schonknecht P, Zimmermann K, Hampel H, Burger K, Otto M, Haustein S, Herzog K, Dannenberg R, Wurster U, Bibl M, Maler JM, Reubach U, Kornhuber J, Wiltfang J (2006) International quality control survey of neurochemical dementia diagnostics. Neurosci Lett 409:1–4PubMedCrossRef Lewczuk P, Beck G, Ganslandt O, Esselmann H, Deisenhammer F, Regeniter A, Petereit HF, Tumani H, Gerritzen A, Oschmann P, Schroder J, Schonknecht P, Zimmermann K, Hampel H, Burger K, Otto M, Haustein S, Herzog K, Dannenberg R, Wurster U, Bibl M, Maler JM, Reubach U, Kornhuber J, Wiltfang J (2006) International quality control survey of neurochemical dementia diagnostics. Neurosci Lett 409:1–4PubMedCrossRef
Zurück zum Zitat Lewczuk P, Kamrowski-Kruck H, Peters O, Heuser I, Jessen F, Popp J, Burger K, Hampel H, Frolich L, Wolf S, Prinz B, Jahn H, Luckhaus C, Perneczky R, Hull M, Schroder J, Kessler H, Pantel J, Gertz H-J, Klafki H-W, Kolsch H, Reulbach U, Esselmann H, Maler JM, Bibl M, Kornhuber J, Wiltfang J (2008) Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer’s disease: a multicenter study. Mol Psychiatry (in press) Lewczuk P, Kamrowski-Kruck H, Peters O, Heuser I, Jessen F, Popp J, Burger K, Hampel H, Frolich L, Wolf S, Prinz B, Jahn H, Luckhaus C, Perneczky R, Hull M, Schroder J, Kessler H, Pantel J, Gertz H-J, Klafki H-W, Kolsch H, Reulbach U, Esselmann H, Maler JM, Bibl M, Kornhuber J, Wiltfang J (2008) Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer’s disease: a multicenter study. Mol Psychiatry (in press)
Zurück zum Zitat Lewczuk P, Wiltfang J (2008) Neurochemical dementia diagnostics: state of the art and research perspectives. Proteomics 8:1292–1301PubMedCrossRef Lewczuk P, Wiltfang J (2008) Neurochemical dementia diagnostics: state of the art and research perspectives. Proteomics 8:1292–1301PubMedCrossRef
Zurück zum Zitat Otto M, Wiltfang J, Cepek L, Neumann M, Mollenhauer B, Steinacker P, Ciesielczyk B, Schulz-Schaeffer W, Kretzschmar HA, Poser S (2002) Tau protein and 14–3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 58:192–197PubMed Otto M, Wiltfang J, Cepek L, Neumann M, Mollenhauer B, Steinacker P, Ciesielczyk B, Schulz-Schaeffer W, Kretzschmar HA, Poser S (2002) Tau protein and 14–3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 58:192–197PubMed
Zurück zum Zitat Portelius E, Brinkmalm G, Tran AJ, Zetterberg H, Westman-Brinkmalm A, Blennow K (2009) Identification of novel APP/Abeta isoforms in human cerebrospinal fluid. Neurodegener Dis 6:87–94PubMedCrossRef Portelius E, Brinkmalm G, Tran AJ, Zetterberg H, Westman-Brinkmalm A, Blennow K (2009) Identification of novel APP/Abeta isoforms in human cerebrospinal fluid. Neurodegener Dis 6:87–94PubMedCrossRef
Zurück zum Zitat Smesny S, Stein S, Willhardt I, Lasch J, Sauer H (2008) Decreased phospholipase A2 activity in cerebrospinal fluid of patients with dementia. J Neural Transm 115:1173–1179PubMedCrossRef Smesny S, Stein S, Willhardt I, Lasch J, Sauer H (2008) Decreased phospholipase A2 activity in cerebrospinal fluid of patients with dementia. J Neural Transm 115:1173–1179PubMedCrossRef
Zurück zum Zitat Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Pericak-Vance M, Schmechel D, Saunders AM, Goldgaber D, Roses AD (1993) Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci USA 90:8098–8102PubMedCrossRef Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Pericak-Vance M, Schmechel D, Saunders AM, Goldgaber D, Roses AD (1993) Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci USA 90:8098–8102PubMedCrossRef
Zurück zum Zitat The Working Group on: “Molecular and Biochemical Markers of Alzheimer’s Disease” (1998) Consensus report of the working group on: “Molecular and Biochemical Markers of Alzheimer’s Disease”. The Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group. Neurobiol Aging 19:109–116CrossRef The Working Group on: “Molecular and Biochemical Markers of Alzheimer’s Disease” (1998) Consensus report of the working group on: “Molecular and Biochemical Markers of Alzheimer’s Disease”. The Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group. Neurobiol Aging 19:109–116CrossRef
Zurück zum Zitat Verwey NA, van der Flier WM, Blennow K, Clark C, Sokolow S, De Deyn PP, Galasko D, Hampel H, Hartmann T, Kapaki E, Lannfelt L, Mehta PD, Parnetti L, Petzold A, Pirttila T, Saleh L, Skinningsrud A, Swieten JC, Verbeek MM, Wiltfang J, Younkin S, Scheltens P, Blankenstein MA (2009) A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer’s disease. Ann Clin Biochem 46:235–240PubMedCrossRef Verwey NA, van der Flier WM, Blennow K, Clark C, Sokolow S, De Deyn PP, Galasko D, Hampel H, Hartmann T, Kapaki E, Lannfelt L, Mehta PD, Parnetti L, Petzold A, Pirttila T, Saleh L, Skinningsrud A, Swieten JC, Verbeek MM, Wiltfang J, Younkin S, Scheltens P, Blankenstein MA (2009) A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer’s disease. Ann Clin Biochem 46:235–240PubMedCrossRef
Zurück zum Zitat Weih M, Krinninger M, Zimmermann R, Lewczuk P, Svitek J, Schaller G, Degirmenci U, Richter-Schmidinger T, Wiltfang J, Kuwert T, Kornhuber J, Schmidt D (2009) Sensitivity of neurochemical dementia diagnostics in CSF compared to 99mTc-SPECT in Alzheimer’s dementia. Fortschr Neurol Psychiatr 77:407–411PubMedCrossRef Weih M, Krinninger M, Zimmermann R, Lewczuk P, Svitek J, Schaller G, Degirmenci U, Richter-Schmidinger T, Wiltfang J, Kuwert T, Kornhuber J, Schmidt D (2009) Sensitivity of neurochemical dementia diagnostics in CSF compared to 99mTc-SPECT in Alzheimer’s dementia. Fortschr Neurol Psychiatr 77:407–411PubMedCrossRef
Zurück zum Zitat Welge V, Fiege O, Lewczuk P, Mollenhauer B, Esselmann H, Klafki HW, Wolf S, Trenkwalder C, Otto M, Kornhuber J, Wiltfang J, Bibl M (2009) Combined CSF tau, p-tau181 and amyloid-beta 38/40/42 for diagnosing Alzheimer’s disease. J Neural Transm 116:203–212PubMedCrossRef Welge V, Fiege O, Lewczuk P, Mollenhauer B, Esselmann H, Klafki HW, Wolf S, Trenkwalder C, Otto M, Kornhuber J, Wiltfang J, Bibl M (2009) Combined CSF tau, p-tau181 and amyloid-beta 38/40/42 for diagnosing Alzheimer’s disease. J Neural Transm 116:203–212PubMedCrossRef
Zurück zum Zitat Wiltfang J, Esselmann H, Bibl M, Hull M, Hampel H, Kessler H, Frolich L, Schroder J, Peters O, Jessen F, Luckhaus C, Perneczky R, Jahn H, Fiszer M, Maler JM, Zimmermann R, Bruckmoser R, Kornhuber J, Lewczuk P (2007) Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load. J Neurochem 101:1053–1059PubMedCrossRef Wiltfang J, Esselmann H, Bibl M, Hull M, Hampel H, Kessler H, Frolich L, Schroder J, Peters O, Jessen F, Luckhaus C, Perneczky R, Jahn H, Fiszer M, Maler JM, Zimmermann R, Bruckmoser R, Kornhuber J, Lewczuk P (2007) Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load. J Neurochem 101:1053–1059PubMedCrossRef
Metadaten
Titel
Neurochemical dementia diagnostics: a simple algorithm for interpretation of the CSF biomarkers
verfasst von
Piotr Lewczuk
Rüdiger Zimmermann
Jens Wiltfang
Johannes Kornhuber
Publikationsdatum
01.09.2009
Verlag
Springer Vienna
Erschienen in
Journal of Neural Transmission / Ausgabe 9/2009
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-009-0277-y

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