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16 results on '"Herukka, S.K."'

1. Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum

Author

Jansen, W.J., Janssen, O., Tijms, B.M., Vos, S.J.B., Ossenkoppele, R., Visser, P.J., Group, A.B.S., Aarsland, D., Alcolea, D., Altomare, D., Arnim, C. von, Baiardi, S., Baldeiras, I., Barthel, H., Bateman, R.J., Berckel, B. Van, Binette, A.P., Blennow, K., Boada, M., Boecker, H., Bottlaender, M., Braber, A., Brooks, D.J., Buchem, M.A. van, Camus, V., Carill, J.M., Cerman, J., Chen, K., Chételat, G., Chipi, E., Cohen, A.D., Daniels, A., Delarue, M., Didic, M., Drzezga, A., Dubois, B., Eckerström, M., Ekblad, L.L., Engelborghs, S., Epelbaum, S., Fagan, A.M., Fan, Y., Fladby, T., Fleisher, A.S., Flier, W.M. van der, Förster, S., Fortea, J., Frederiksen, K.S., Freund-Levi, Y., Frings, L., Frisoni, G.B., Fröhlich, L., Gabryelewicz, T., Gertz, H.J., Gill, K.D., Gkatzima, O., Gómez-Tortosa, E., Grimmer, T., Guedj, E., Habeck, C.G., Hampel, H., Handels, R., Hansson, O., Hausner, L., Hellwig, S., Heneka, M.T., Herukka, S.K., Hildebrandt, H., Hodges, J., Hort, J., Huang, C.C., Iriondo, A.J., Itoh, Y., Ivanoiu, A., Jagust, W.J., Jessen, F., Johannsen, P., Johnson, K.A., Kandimalla, R., Kapaki, E.N., Kern, S., Kilander, L., Klimkowicz-Mrowiec, A., Klunk, W.E., Koglin, N., Kornhuber, J., Kramberger, M.G., Kuo, H.C., Laere, K. Van, Landau, S.M., Landeau, B., Lee, Dyantha I. van der, Leon, M., Leyton, C.E., Lin, K.J., Lleó, A., Löwenmark, M., Madsen, K., Maier, W., Marcusson, J., Olde Rikkert, M.G.M., Verbeek, M.M., Zboch, M., Zetterberg, H., Jansen, W.J., Janssen, O., Tijms, B.M., Vos, S.J.B., Ossenkoppele, R., Visser, P.J., Group, A.B.S., Aarsland, D., Alcolea, D., Altomare, D., Arnim, C. von, Baiardi, S., Baldeiras, I., Barthel, H., Bateman, R.J., Berckel, B. Van, Binette, A.P., Blennow, K., Boada, M., Boecker, H., Bottlaender, M., Braber, A., Brooks, D.J., Buchem, M.A. van, Camus, V., Carill, J.M., Cerman, J., Chen, K., Chételat, G., Chipi, E., Cohen, A.D., Daniels, A., Delarue, M., Didic, M., Drzezga, A., Dubois, B., Eckerström, M., Ekblad, L.L., Engelborghs, S., Epelbaum, S., Fagan, A.M., Fan, Y., Fladby, T., Fleisher, A.S., Flier, W.M. van der, Förster, S., Fortea, J., Frederiksen, K.S., Freund-Levi, Y., Frings, L., Frisoni, G.B., Fröhlich, L., Gabryelewicz, T., Gertz, H.J., Gill, K.D., Gkatzima, O., Gómez-Tortosa, E., Grimmer, T., Guedj, E., Habeck, C.G., Hampel, H., Handels, R., Hansson, O., Hausner, L., Hellwig, S., Heneka, M.T., Herukka, S.K., Hildebrandt, H., Hodges, J., Hort, J., Huang, C.C., Iriondo, A.J., Itoh, Y., Ivanoiu, A., Jagust, W.J., Jessen, F., Johannsen, P., Johnson, K.A., Kandimalla, R., Kapaki, E.N., Kern, S., Kilander, L., Klimkowicz-Mrowiec, A., Klunk, W.E., Koglin, N., Kornhuber, J., Kramberger, M.G., Kuo, H.C., Laere, K. Van, Landau, S.M., Landeau, B., Lee, Dyantha I. van der, Leon, M., Leyton, C.E., Lin, K.J., Lleó, A., Löwenmark, M., Madsen, K., Maier, W., Marcusson, J., Olde Rikkert, M.G.M., Verbeek, M.M., Zboch, M., and Zetterberg, H.

Abstract

Contains fulltext : 248802.pdf (Publisher’s version ) (Closed access)

Published
2022

2. Prevalence of the apolipoprotein E epsilon4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease

Author

Mattsson, N., Groot, C. de, Jansen, W.J., Landau, S.M., Villemagne, V.L., Engelborghs, S., Mintun, M.M., Lleo, A., Molinuevo, J.L., Jagust, W.J., Frisoni, G.B., Ivanoiu, A., Chetelat, G., Oliveira, C. de, Rodrigue, K.M., Kornhuber, J., Wallin, A., Klimkowicz-Mrowiec, A., Kandimalla, R., Popp, J., Aalten, P.P., Aarsland, D., Alcolea, D., Almdahl, I.S., Baldeiras, I., Buchem, M.A. van, Cavedo, E., Chen, K., Cohen, A.D., Forster, S., Fortea, J., Frederiksen, K.S., Freund-Levi, Y., Gill, K.D., Gkatzima, O., Grimmer, T., Hampel, H., Herukka, S.K., Johannsen, P., Laere, K. Van, Leon, M.J. de, Maier, W., Marcusson, J., Meulenbroek, O.V., Mollergard, H.M., Morris, J.C., Mroczko, B., Nordlund, A., Prabhakar, S., Peters, O., Rami, L., Rodriguez-Rodriguez, E., Roe, C.M., Ruther, E., Santana, I., Schroder, J., Seo, S.W., Soininen, H., Spiru, L., Stomrud, E., Struyfs, H., Teunissen, C.E., Verhey, F.R.J., Vos, S.J.B., Waalwijk van Doorn, L.L.C. van, Waldemar, G., Wallin, A.K., Wiltfang, J., Vandenberghe, R., Brooks, D.J., Fladby, T., Rowe, C.C., Drzezga, A., Verbeek, M.M., Sarazin, M., Wolk, D.A., Fleisher, A.S., Klunk, W.E., Na, D.L., Sanchez-Juan, P., Lee, D.Y., Nordberg, A., Tsolaki, M., Camus, V., Rinne, J.O., Fagan, A.M., Zetterberg, H., Blennow, K., Rabinovici, G.D., Hansson, O., Berckel, B.N. van, Flier, W.M. van der, Scheltens, P., Visser, P.J., Ossenkoppele, R., Mattsson, N., Groot, C. de, Jansen, W.J., Landau, S.M., Villemagne, V.L., Engelborghs, S., Mintun, M.M., Lleo, A., Molinuevo, J.L., Jagust, W.J., Frisoni, G.B., Ivanoiu, A., Chetelat, G., Oliveira, C. de, Rodrigue, K.M., Kornhuber, J., Wallin, A., Klimkowicz-Mrowiec, A., Kandimalla, R., Popp, J., Aalten, P.P., Aarsland, D., Alcolea, D., Almdahl, I.S., Baldeiras, I., Buchem, M.A. van, Cavedo, E., Chen, K., Cohen, A.D., Forster, S., Fortea, J., Frederiksen, K.S., Freund-Levi, Y., Gill, K.D., Gkatzima, O., Grimmer, T., Hampel, H., Herukka, S.K., Johannsen, P., Laere, K. Van, Leon, M.J. de, Maier, W., Marcusson, J., Meulenbroek, O.V., Mollergard, H.M., Morris, J.C., Mroczko, B., Nordlund, A., Prabhakar, S., Peters, O., Rami, L., Rodriguez-Rodriguez, E., Roe, C.M., Ruther, E., Santana, I., Schroder, J., Seo, S.W., Soininen, H., Spiru, L., Stomrud, E., Struyfs, H., Teunissen, C.E., Verhey, F.R.J., Vos, S.J.B., Waalwijk van Doorn, L.L.C. van, Waldemar, G., Wallin, A.K., Wiltfang, J., Vandenberghe, R., Brooks, D.J., Fladby, T., Rowe, C.C., Drzezga, A., Verbeek, M.M., Sarazin, M., Wolk, D.A., Fleisher, A.S., Klunk, W.E., Na, D.L., Sanchez-Juan, P., Lee, D.Y., Nordberg, A., Tsolaki, M., Camus, V., Rinne, J.O., Fagan, A.M., Zetterberg, H., Blennow, K., Rabinovici, G.D., Hansson, O., Berckel, B.N. van, Flier, W.M. van der, Scheltens, P., Visser, P.J., and Ossenkoppele, R.

Abstract

Item does not contain fulltext, INTRODUCTION: Apolipoprotein E (APOE) epsilon4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta (Abeta) pathology. METHODS: We included 3451 Abeta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon4 prevalence in relation to age, sex, education, and geographical location. RESULTS: The APOE epsilon4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Abeta+ cognitively normal and Abeta+ mild cognitive impairment (P < .05) but not in Abeta+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education. DISCUSSION: The APOE epsilon4 prevalence in AD was higher than that in previous studies, which did not require presence of Abeta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.

Published
2018

3. White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation

Author

Teunissen, C.E., Otto, M., Engelborghs, S., Herukka, S.K., Lehmann, S., Lewczuk, P., Lleó, A., Perret-Liaudet, A., Tumani, H., Turner, M.R., Verbeek, M.M., Wiltfang, J., Zetterberg, H., Parnetti, L., Blennow, K., Teunissen, C.E., Otto, M., Engelborghs, S., Herukka, S.K., Lehmann, S., Lewczuk, P., Lleó, A., Perret-Liaudet, A., Tumani, H., Turner, M.R., Verbeek, M.M., Wiltfang, J., Zetterberg, H., Parnetti, L., and Blennow, K.

Abstract

Contains fulltext : 190996.pdf (publisher's version ) (Open Access)

Published
2018

4. Association of Cerebral Amyloid-beta Aggregation With Cognitive Functioning in Persons Without Dementia

Author

Jansen, W.J., Ossenkoppele, R., Tijms, B.M., Fagan, A.M., Hansson, O., Klunk, W.E., Flier, W.M. van der, Villemagne, V.L., Frisoni, G.B., Fleisher, A.S., Lleo, A., Mintun, M.A., Wallin, A., Engelborghs, S., Na, D.L., Chetelat, G., Molinuevo, J.L., Landau, S.M., Mattsson, N., Kornhuber, J., Sabri, O., Rowe, C.C., Parnetti, L., Popp, J., Fladby, T., Jagust, W.J., Aalten, P., Lee, D.Y., Vandenberghe, R., Oliveira, C. de, Kapaki, E., Froelich, L., Ivanoiu, A., Gabryelewicz, T., Verbeek, M.M., Sanchez-Juan, P., Hildebrandt, H., Camus, V., Zboch, M., Brooks, D.J., Drzezga, A., Rinne, J.O., Newberg, A., Mendonca, A. de, Sarazin, M., Rabinovici, G.D., Madsen, K., Kramberger, M.G., Nordberg, A., Mok, V., Mroczko, B., Wolk, D.A., Meyer, P.T., Tsolaki, M., Scheltens, P., Verhey, F.R.J., Visser, P.J., Aarsland, D., Alcolea, D., Alexander, M., Almdahl, I.S., Arnold, S.E., Baldeiras, I., Barthel, H., Berckel, B.N. van, Blennow, K., Buchem, M.A. van, Cavedo, E., Chen, K., Chipi, E., Cohen, A.D., Forster, S., Fortea, J., Frederiksen, K.S., Freund-Levi, Y., Gkatzima, O., Gordon, M.F., Grimmer, T., Hampel, H., Hausner, L., Hellwig, S., Herukka, S.K., Johannsen, P., Klimkowicz-Mrowiec, A., Kohler, S., Koglin, N., Laere, K. Van, Leon, M., Lisetti, V., Maier, W., Marcusson, J., Meulenbroek, O., Mollergard, H.M., Morris, J.C., Nordlund, A., Novak, G.P., Paraskevas, G.P., Perera, G., Peters, O., Ramakers, I., et al., Jansen, W.J., Ossenkoppele, R., Tijms, B.M., Fagan, A.M., Hansson, O., Klunk, W.E., Flier, W.M. van der, Villemagne, V.L., Frisoni, G.B., Fleisher, A.S., Lleo, A., Mintun, M.A., Wallin, A., Engelborghs, S., Na, D.L., Chetelat, G., Molinuevo, J.L., Landau, S.M., Mattsson, N., Kornhuber, J., Sabri, O., Rowe, C.C., Parnetti, L., Popp, J., Fladby, T., Jagust, W.J., Aalten, P., Lee, D.Y., Vandenberghe, R., Oliveira, C. de, Kapaki, E., Froelich, L., Ivanoiu, A., Gabryelewicz, T., Verbeek, M.M., Sanchez-Juan, P., Hildebrandt, H., Camus, V., Zboch, M., Brooks, D.J., Drzezga, A., Rinne, J.O., Newberg, A., Mendonca, A. de, Sarazin, M., Rabinovici, G.D., Madsen, K., Kramberger, M.G., Nordberg, A., Mok, V., Mroczko, B., Wolk, D.A., Meyer, P.T., Tsolaki, M., Scheltens, P., Verhey, F.R.J., Visser, P.J., Aarsland, D., Alcolea, D., Alexander, M., Almdahl, I.S., Arnold, S.E., Baldeiras, I., Barthel, H., Berckel, B.N. van, Blennow, K., Buchem, M.A. van, Cavedo, E., Chen, K., Chipi, E., Cohen, A.D., Forster, S., Fortea, J., Frederiksen, K.S., Freund-Levi, Y., Gkatzima, O., Gordon, M.F., Grimmer, T., Hampel, H., Hausner, L., Hellwig, S., Herukka, S.K., Johannsen, P., Klimkowicz-Mrowiec, A., Kohler, S., Koglin, N., Laere, K. Van, Leon, M., Lisetti, V., Maier, W., Marcusson, J., Meulenbroek, O., Mollergard, H.M., Morris, J.C., Nordlund, A., Novak, G.P., Paraskevas, G.P., Perera, G., Peters, O., and Ramakers, I., et al.

Abstract

Contains fulltext : 190311.pdf (Publisher’s version ) (Closed access), Importance: Cerebral amyloid-beta aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials. Objective: To investigate whether amyloid-beta aggregation is associated with cognitive functioning in persons without dementia. Design, Setting, and Participants: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017. Main Outcomes and Measures: Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score

Published
2018

5. Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers

Author

Matos, Mafalda Ramos de, Ferreira, C., Herukka, S.K., Soininen, H., Janeiro, A.M., Santana, I., Verbeek, M.M., Mendonca, A. de, Martins, M., Meulenbroek, O.V., Matos, Mafalda Ramos de, Ferreira, C., Herukka, S.K., Soininen, H., Janeiro, A.M., Santana, I., Verbeek, M.M., Mendonca, A. de, Martins, M., and Meulenbroek, O.V.

Abstract

Item does not contain fulltext

Published
2018

6. Association Between Later Life Lifestyle Factors and Alzheimer's Disease Biomarkers in Non-Demented Individuals: A Longitudinal Descriptive Cohort Study

Author

Reijs, B.L., Vos, S.J., Soininen, H., Lötjonen, J., Koikkalainen, J., Pikkarainen, M., Hall, A., Vanninen, R., Liu, Y., Herukka, S.K., Freund-Levi, Y., Frisoni, G.B., Frölich, G.B., Nobili, F.M., Olde Rikkert, M.G.M., Spiru, L., Tsolaki, M., Wallin, A.K., Scheltens, P., Verhey, F.R.J., Visser, P.J., Reijs, B.L., Vos, S.J., Soininen, H., Lötjonen, J., Koikkalainen, J., Pikkarainen, M., Hall, A., Vanninen, R., Liu, Y., Herukka, S.K., Freund-Levi, Y., Frisoni, G.B., Frölich, G.B., Nobili, F.M., Olde Rikkert, M.G.M., Spiru, L., Tsolaki, M., Wallin, A.K., Scheltens, P., Verhey, F.R.J., and Visser, P.J.

Abstract

Item does not contain fulltext

Published
2017

7. Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes

Author

Waalwijk van Doorn, L.L.C. van, Gispert, J.D., Kuiperij, H.B., Claassen, J.A.H.R., Arighi, A., Baldeiras, I., Blennow, K., Bozzali, M., Castelo-Branco, M., Cavedo, E., Emek-Savas, D.D., Eren, E., Eusebi, P., Farotti, L., Fenoglio, C., Ormaechea, J.F., Freund-Levi, Y., Frisoni, G.B., Galimberti, D., Genc, S., Greco, V., Hampel, H., Herukka, S.K., Liu, Y., Llado, A., Lleo, A., Nobili, F.M., Oguz, K.K., Parnetti, L., Pereira, J., Picco, A., Pikkarainen, M., Oliveira, C.R., Saka, E., Salvadori, N., Sanchez-Valle, R., Santana, I., Scarpini, E., Scheltens, P., Soininen, H., Tarducci, R., Teunissen, C., Tsolaki, M., Urbani, A., Vilaplana, E., Visser, P.J., Wallin, A.K., Yener, G., Molinuevo, J.L., Meulenbroek, O.V., Verbeek, M.M., Waalwijk van Doorn, L.L.C. van, Gispert, J.D., Kuiperij, H.B., Claassen, J.A.H.R., Arighi, A., Baldeiras, I., Blennow, K., Bozzali, M., Castelo-Branco, M., Cavedo, E., Emek-Savas, D.D., Eren, E., Eusebi, P., Farotti, L., Fenoglio, C., Ormaechea, J.F., Freund-Levi, Y., Frisoni, G.B., Galimberti, D., Genc, S., Greco, V., Hampel, H., Herukka, S.K., Liu, Y., Llado, A., Lleo, A., Nobili, F.M., Oguz, K.K., Parnetti, L., Pereira, J., Picco, A., Pikkarainen, M., Oliveira, C.R., Saka, E., Salvadori, N., Sanchez-Valle, R., Santana, I., Scarpini, E., Scheltens, P., Soininen, H., Tarducci, R., Teunissen, C., Tsolaki, M., Urbani, A., Vilaplana, E., Visser, P.J., Wallin, A.K., Yener, G., Molinuevo, J.L., Meulenbroek, O.V., and Verbeek, M.M.

Abstract

Item does not contain fulltext, Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., Abeta42, total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF Abeta42 levels inversely correlated to VV/TIV in the whole study population (Abeta42: r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF Abeta42 alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF Abeta42 levels.

Published
2017

8. Comparison of Different Matrices as Potential Quality Control Samples for Neurochemical Dementia Diagnostics

Author

Lelental, N., Brandner, S., Kofanova, O., Blennow, K., Zetterberg, H., Andreasson, U., Engelborghs, S., Mroczko, B., Gabryelewicz, T., Teunissen, C., Mollenhauer, B., Parnetti, L., Chiasserini, D., Molinuevo, J.L., Perret-Liaudet, A., Verbeek, M.M., Andreasen, N., Brosseron, F., Bahl, J.M., Herukka, S.K., Hausner, L., Frolich, L., Labonte, A., Poirier, J., Miller, A.M., Zilka, N., Kovacech, B., Urbani, A., Suardi, S., Oliveira, C. de, Baldeiras, I., Dubois, B., Rot, U., Lehmann, S., Skinningsrud, A., Betsou, F., Wiltfang, J., Gkatzima, O., Winblad, B., Buchfelder, M., Kornhuber, J., Lewczuk, P., Lelental, N., Brandner, S., Kofanova, O., Blennow, K., Zetterberg, H., Andreasson, U., Engelborghs, S., Mroczko, B., Gabryelewicz, T., Teunissen, C., Mollenhauer, B., Parnetti, L., Chiasserini, D., Molinuevo, J.L., Perret-Liaudet, A., Verbeek, M.M., Andreasen, N., Brosseron, F., Bahl, J.M., Herukka, S.K., Hausner, L., Frolich, L., Labonte, A., Poirier, J., Miller, A.M., Zilka, N., Kovacech, B., Urbani, A., Suardi, S., Oliveira, C. de, Baldeiras, I., Dubois, B., Rot, U., Lehmann, S., Skinningsrud, A., Betsou, F., Wiltfang, J., Gkatzima, O., Winblad, B., Buchfelder, M., Kornhuber, J., and Lewczuk, P.

Abstract

Item does not contain fulltext, BACKGROUND: Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples. OBJECTIVE: To prepare and test alternative matrices for QC samples that could facilitate intra- and inter-laboratory QC of the NDD biomarkers. METHODS: Three matrices were validated in this study: (A) human pooled CSF, (B) Abeta peptides spiked into human prediluted plasma, and (C) Abeta peptides spiked into solution of bovine serum albumin in phosphate-buffered saline. All matrices were tested also after supplementation with an antibacterial agent (sodium azide). We analyzed short- and long-term stability of the biomarkers with ELISA and chemiluminescence (Fujirebio Europe, MSD, IBL International), and performed an inter-laboratory variability study. RESULTS: NDD biomarkers turned out to be stable in almost all samples stored at the tested conditions for up to 14 days as well as in samples stored deep-frozen (at - 80 degrees C) for up to one year. Sodium azide did not influence biomarker stability. Inter-center variability of the samples sent at room temperature (pooled CSF, freeze-dried CSF, and four artificial matrices) was comparable to the results obtained on deep-frozen samples in other large-scale projects. CONCLUSION: Our results suggest that it is possible to replace self-made, CSF-based QC samples with large-scale volumes of QC materials prepared with artificial peptides and matrices. This would greatly facilitate intra- and inter-laboratory QC schedules for NDD measurements.

Published
2016

9. The utility of alpha-synuclein as biofluid marker in neurodegenerative diseases: a systematic review of the literature

Author

Simonsen, A.H., Kuiperij, B., El-Agnaf, O.M., Engelborghs, S., Herukka, S.K., Parnetti, L., Rektorova, I., Vanmechelen, E., Kapaki, E., Verbeek, M.M., Mollenhauer, B., Simonsen, A.H., Kuiperij, B., El-Agnaf, O.M., Engelborghs, S., Herukka, S.K., Parnetti, L., Rektorova, I., Vanmechelen, E., Kapaki, E., Verbeek, M.M., and Mollenhauer, B.

Abstract

Item does not contain fulltext, The discovery of alpha-synuclein (alpha-syn) as a major component of Lewy bodies, neuropathological hallmark of Parkinson's disease (PD), dementia with Lewy bodies and of glial inclusions in multiple system atrophy initiated the investigation of alpha-syn as a biomarker in cerebrospinal fluid (CSF). Due to the involvement of the periphery in PD the quantification of alpha-syn in peripheral fluids such as serum, plasma and saliva has been investigated as well. We review how the development of multiple assays for the quantification of alpha-syn has yielded novel insights into the variety of alpha-syn species present in the different fluids; the optimal preanalytical conditions required for robust quantification and the potential clinical value of alpha-syn as biomarker. We also suggest future approaches to use of CSF alpha-syn in neurodegenerative diseases.

Published
2016

10. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis

Author

Jansen, W.J., Ossenkoppele, R., Knol, D.L., Tijms, B.M., Scheltens, P.J., Verhey, F.R.J., Visser, P.J., Aalten, P., Aarsland, D., Alcolea, D., Alexander, M., Almdahl, I.S., Arnold, S.E., Baldeiras, I., Barthel, H., Berckel, B.N. van, Bibeau, K., Blennow, K., Brooks, D.J., Buchem, M.A. van, Camus, V., Cavedo, E., Chen, K., Chetelat, G., Cohen, A.D., Drzezga, A., Engelborghs, S., Fagan, A.M., Fladby, T., Fleisher, A.S., Flier, W.M. van der, Ford, L., Forster, S., Fortea, J., Foskett, N., Frederiksen, K.S., Freund-Levi, Y., Frisoni, G.B., Froelich, L., Gabryelewicz, T., Gill, K.D., Gkatzima, O., Gomez-Tortosa, E., Gordon, M.F., Grimmer, T., Hampel, H., Hausner, L., Hellwig, S., Herukka, S.K., Hildebrandt, H., Ishihara, L., Ivanoiu, A., Jagust, W.J., Johannsen, P., Kandimalla, R., Kapaki, E., Klimkowicz-Mrowiec, A., Klunk, W.E., Kohler, S., Koglin, N., Kornhuber, J., Kramberger, M.G., Laere, K. Van, Landau, S.M., Lee, D.Y., Leon, M., Lisetti, V., Lleo, A., Madsen, K., Maier, W., Marcusson, J., Mattsson, N., Mendonca, A. de, Meulenbroek, O.V., Meyer, P.T., Mintun, M.A., Mok, V., Molinuevo, J.L., Mollergard, H.M., Morris, J.C., Mroczko, B., Mussele, S. Van der, Na, D.L., Newberg, A., Nordberg, A., Nordlund, A., Novak, G.P., Paraskevas, G.P., Parnetti, L., Perera, G., Peters, O., Popp, J., Prabhakar, S., Rabinovici, G.D., Ramakers, I.H., Rami, L., Oliveira, C.R., Rinne, J.O., Rodrigue, K.M., Rodriguez-Rodriguez, E., Verbeek, M.M., et al., Jansen, W.J., Ossenkoppele, R., Knol, D.L., Tijms, B.M., Scheltens, P.J., Verhey, F.R.J., Visser, P.J., Aalten, P., Aarsland, D., Alcolea, D., Alexander, M., Almdahl, I.S., Arnold, S.E., Baldeiras, I., Barthel, H., Berckel, B.N. van, Bibeau, K., Blennow, K., Brooks, D.J., Buchem, M.A. van, Camus, V., Cavedo, E., Chen, K., Chetelat, G., Cohen, A.D., Drzezga, A., Engelborghs, S., Fagan, A.M., Fladby, T., Fleisher, A.S., Flier, W.M. van der, Ford, L., Forster, S., Fortea, J., Foskett, N., Frederiksen, K.S., Freund-Levi, Y., Frisoni, G.B., Froelich, L., Gabryelewicz, T., Gill, K.D., Gkatzima, O., Gomez-Tortosa, E., Gordon, M.F., Grimmer, T., Hampel, H., Hausner, L., Hellwig, S., Herukka, S.K., Hildebrandt, H., Ishihara, L., Ivanoiu, A., Jagust, W.J., Johannsen, P., Kandimalla, R., Kapaki, E., Klimkowicz-Mrowiec, A., Klunk, W.E., Kohler, S., Koglin, N., Kornhuber, J., Kramberger, M.G., Laere, K. Van, Landau, S.M., Lee, D.Y., Leon, M., Lisetti, V., Lleo, A., Madsen, K., Maier, W., Marcusson, J., Mattsson, N., Mendonca, A. de, Meulenbroek, O.V., Meyer, P.T., Mintun, M.A., Mok, V., Molinuevo, J.L., Mollergard, H.M., Morris, J.C., Mroczko, B., Mussele, S. Van der, Na, D.L., Newberg, A., Nordberg, A., Nordlund, A., Novak, G.P., Paraskevas, G.P., Parnetti, L., Perera, G., Peters, O., Popp, J., Prabhakar, S., Rabinovici, G.D., Ramakers, I.H., Rami, L., Oliveira, C.R., Rinne, J.O., Rodrigue, K.M., Rodriguez-Rodriguez, E., Verbeek, M.M., and et al.

Abstract

Item does not contain fulltext, IMPORTANCE: Cerebral amyloid-beta aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). DATA SOURCES: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. STUDY SELECTION: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. DATA EXTRACTION AND SYNTHESIS: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. MAIN OUTCOMES AND MEASURES: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. RESULTS: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-epsilon4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE epsilon4epsilon4 carriers, 50 years for epsilon2epsilon4 carriers, 55 years for epsilon3epsilon4 c

Published
2015

11. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.

Author

Amyloid Biomarker Study Group, Jansen, W.J., Ossenkoppele, R., Knol, D.L., Tijms, B.M., Scheltens, P., Verhey, F.R., Visser, P.J., Aalten, P., Aarsland, D., Alcolea, D., Alexander, M., Almdahl, I.S., Arnold, S.E., Baldeiras, I., Barthel, H., van Berckel, B.N., Bibeau, K., Blennow, K., Brooks, D.J., van Buchem, M.A., Camus, V., Cavedo, E., Chen, K., Chetelat, G., Cohen, A.D., Drzezga, A., Engelborghs, S., Fagan, A.M., Fladby, T., Fleisher, A.S., van der Flier, W.M., Ford, L., Förster, S., Fortea, J., Foskett, N., Frederiksen, K.S., Freund-Levi, Y., Frisoni, G.B., Froelich, L., Gabryelewicz, T., Gill, K.D., Gkatzima, O., Gómez-Tortosa, E., Gordon, M.F., Grimmer, T., Hampel, H., Hausner, L., Hellwig, S., Herukka, S.K., Hildebrandt, H., Ishihara, L., Ivanoiu, A., Jagust, W.J., Johannsen, P., Kandimalla, R., Kapaki, E., Klimkowicz-Mrowiec, A., Klunk, W.E., Köhler, S., Koglin, N., Kornhuber, J., Kramberger, M.G., Van Laere, K., Landau, S.M., Lee, D.Y., de Leon, M., Lisetti, V., Lleó, A., Madsen, K., Maier, W., Marcusson, J., Mattsson, N., de Mendonça, A., Meulenbroek, O., Meyer, P.T., Mintun, M.A., Mok, V., Molinuevo, J.L., Møllergård, H.M., Morris, J.C., Mroczko, B., Van der Mussele, S., Na, D.L., Newberg, A., Nordberg, A., Nordlund, A., Novak, G.P., Paraskevas, G.P., Parnetti, L., Perera, G., Peters, O., Popp, J., Prabhakar, S., Rabinovici, G.D., Ramakers, I.H., Rami, L., Resende de Oliveira, C., Rinne, J.O., Rodrigue, K.M., Rodríguez-Rodríguez, E., Roe, C.M., Rot, U., Rowe, C.C., Rüther, E., Sabri, O., Sanchez-Juan, P., Santana, I., Sarazin, M., Schröder, J., Schütte, C., Seo, S.W., Soetewey, F., Soininen, H., Spiru, L., Struyfs, H., Teunissen, C.E., Tsolaki, M., Vandenberghe, R., Verbeek, M.M., Villemagne, V.L., Vos, S.J., van Waalwijk van Doorn, L.J., Waldemar, G., Wallin, A., Wallin, Å.K., Wiltfang, J., Wolk, D.A., Zboch, M., Zetterberg, H., Amyloid Biomarker Study Group, Jansen, W.J., Ossenkoppele, R., Knol, D.L., Tijms, B.M., Scheltens, P., Verhey, F.R., Visser, P.J., Aalten, P., Aarsland, D., Alcolea, D., Alexander, M., Almdahl, I.S., Arnold, S.E., Baldeiras, I., Barthel, H., van Berckel, B.N., Bibeau, K., Blennow, K., Brooks, D.J., van Buchem, M.A., Camus, V., Cavedo, E., Chen, K., Chetelat, G., Cohen, A.D., Drzezga, A., Engelborghs, S., Fagan, A.M., Fladby, T., Fleisher, A.S., van der Flier, W.M., Ford, L., Förster, S., Fortea, J., Foskett, N., Frederiksen, K.S., Freund-Levi, Y., Frisoni, G.B., Froelich, L., Gabryelewicz, T., Gill, K.D., Gkatzima, O., Gómez-Tortosa, E., Gordon, M.F., Grimmer, T., Hampel, H., Hausner, L., Hellwig, S., Herukka, S.K., Hildebrandt, H., Ishihara, L., Ivanoiu, A., Jagust, W.J., Johannsen, P., Kandimalla, R., Kapaki, E., Klimkowicz-Mrowiec, A., Klunk, W.E., Köhler, S., Koglin, N., Kornhuber, J., Kramberger, M.G., Van Laere, K., Landau, S.M., Lee, D.Y., de Leon, M., Lisetti, V., Lleó, A., Madsen, K., Maier, W., Marcusson, J., Mattsson, N., de Mendonça, A., Meulenbroek, O., Meyer, P.T., Mintun, M.A., Mok, V., Molinuevo, J.L., Møllergård, H.M., Morris, J.C., Mroczko, B., Van der Mussele, S., Na, D.L., Newberg, A., Nordberg, A., Nordlund, A., Novak, G.P., Paraskevas, G.P., Parnetti, L., Perera, G., Peters, O., Popp, J., Prabhakar, S., Rabinovici, G.D., Ramakers, I.H., Rami, L., Resende de Oliveira, C., Rinne, J.O., Rodrigue, K.M., Rodríguez-Rodríguez, E., Roe, C.M., Rot, U., Rowe, C.C., Rüther, E., Sabri, O., Sanchez-Juan, P., Santana, I., Sarazin, M., Schröder, J., Schütte, C., Seo, S.W., Soetewey, F., Soininen, H., Spiru, L., Struyfs, H., Teunissen, C.E., Tsolaki, M., Vandenberghe, R., Verbeek, M.M., Villemagne, V.L., Vos, S.J., van Waalwijk van Doorn, L.J., Waldemar, G., Wallin, A., Wallin, Å.K., Wiltfang, J., Wolk, D.A., Zboch, M., and Zetterberg, H.

Abstract

IMPORTANCE: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). DATA SOURCES: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. STUDY SELECTION: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. DATA EXTRACTION AND SYNTHESIS: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. MAIN OUTCOMES AND MEASURES: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. RESULTS: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 y

Published
2015

12. Age and diagnostic performance of Alzheimer disease CSF biomarkers.

Author

Mattsson, N., Rosen, E., Hansson, O., Andreasen, N., Parnetti, L., Jonsson, M., Herukka, S.K., Flier, W.M. van der, Blankenstein, M.A., Ewers, M., Rich, K., Kaiser, E., Verbeek, M.M., Olde Rikkert, M., Tsolaki, M., Mulugeta, E., Aarsland, D., Visser, P.J., Schroder, J., Marcusson, J., Leon, M., Hampel, H., Scheltens, P., Wallin, A., Eriksdotter-Jonhagen, M., Minthon, L., Winblad, B., Blennow, K., Zetterberg, H., Mattsson, N., Rosen, E., Hansson, O., Andreasen, N., Parnetti, L., Jonsson, M., Herukka, S.K., Flier, W.M. van der, Blankenstein, M.A., Ewers, M., Rich, K., Kaiser, E., Verbeek, M.M., Olde Rikkert, M., Tsolaki, M., Mulugeta, E., Aarsland, D., Visser, P.J., Schroder, J., Marcusson, J., Leon, M., Hampel, H., Scheltens, P., Wallin, A., Eriksdotter-Jonhagen, M., Minthon, L., Winblad, B., Blennow, K., and Zetterberg, H.

Abstract

Item does not contain fulltext, OBJECTIVES: Core CSF changes in Alzheimer disease (AD) are decreased amyloid beta(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. METHODS: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis. RESULTS: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. CONCLUSION: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations.

Published
2012

13. The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers

Author

Mattsson, N., Andreasson, U., Persson, S., Arai, H., Batish, S.D., Bernardini, S., Bocchio-Chiavetto, L., Blankenstein, M.A., Carrillo, M.C., Chalbot, S., Coart, E., Chiasserini, D., Cutler, N., Dahlfors, G., Duller, S., Fagan, A.M., Forlenza, O., Frisoni, G.B., Galasko, D., Galimberti, D., Hampel, H., Handberg, A., Heneka, M.T., Herskovits, A.Z., Herukka, S.K., Holtzman, D.M., Humpel, C., Hyman, B.T., Iqbal, K., Jucker, M., Kaeser, S.A., Kaiser, E., Kapaki, E., Kidd, D., Klivenyi, P., Knudsen, C.S., Kummer, M.P., Lui, J., Llado, A., Lewczuk, P., Li, Q.X., Martins, R., Masters, C., McAuliffe, J., Mercken, M., Moghekar, A., Molinuevo, J.L., Montine, T.J., Nowatzke, W., O'Brien, R., Otto, M., Paraskevas, G.P., Parnetti, L., Petersen, R.C., Prvulovic, D., Reus, H.P.M. de, Rissman, R.A., Scarpini, E., Stefani, A., Soininen, H., Schroder, J., Shaw, L.M., Skinningsrud, A., Skrogstad, B., Spreer, A., Talib, L., Teunissen, C., Trojanowski, J.Q., Tumani, H., Umek, R.M., Broeck, B. Van, Vanderstichele, H., Vecsei, L., Verbeek, M.M., Windisch, M., Zhang, J., Zetterberg, H., Blennow, K., Mattsson, N., Andreasson, U., Persson, S., Arai, H., Batish, S.D., Bernardini, S., Bocchio-Chiavetto, L., Blankenstein, M.A., Carrillo, M.C., Chalbot, S., Coart, E., Chiasserini, D., Cutler, N., Dahlfors, G., Duller, S., Fagan, A.M., Forlenza, O., Frisoni, G.B., Galasko, D., Galimberti, D., Hampel, H., Handberg, A., Heneka, M.T., Herskovits, A.Z., Herukka, S.K., Holtzman, D.M., Humpel, C., Hyman, B.T., Iqbal, K., Jucker, M., Kaeser, S.A., Kaiser, E., Kapaki, E., Kidd, D., Klivenyi, P., Knudsen, C.S., Kummer, M.P., Lui, J., Llado, A., Lewczuk, P., Li, Q.X., Martins, R., Masters, C., McAuliffe, J., Mercken, M., Moghekar, A., Molinuevo, J.L., Montine, T.J., Nowatzke, W., O'Brien, R., Otto, M., Paraskevas, G.P., Parnetti, L., Petersen, R.C., Prvulovic, D., Reus, H.P.M. de, Rissman, R.A., Scarpini, E., Stefani, A., Soininen, H., Schroder, J., Shaw, L.M., Skinningsrud, A., Skrogstad, B., Spreer, A., Talib, L., Teunissen, C., Trojanowski, J.Q., Tumani, H., Umek, R.M., Broeck, B. Van, Vanderstichele, H., Vecsei, L., Verbeek, M.M., Windisch, M., Zhang, J., Zetterberg, H., and Blennow, K.

Abstract

Contains fulltext : 98400.pdf (publisher's version ) (Closed access), BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid beta (Abeta)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. METHODS: The program is open for laboratories using commercially available kits for Abeta, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. RESULTS: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Abeta-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Abeta triplex (AbetaN-42, AbetaN-40, and AbetaN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. CONCLUSIONS: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.

Published
2011

14. Neurofilament ELISA validation.

Author

Petzold, A., Altintas, A., Andreoni, L., Bartos, A., Berthele, A., Blankenstein, M.A., Buee, L., Castellazzi, M., Cepok, S., Comabella, M., Constantinescu, C.S., Deisenhammer, F., Deniz, G., Erten, G., Espino, M., Fainardi, E., Franciotta, D., Freedman, M.S., Giedraitis, V., Gilhus, N.E., Giovannoni, G., Glabinski, A., Grieb, P., Hartung, H.P., Hemmer, B., Herukka, S.K., Hintzen, R., Ingelsson, M., Jackson, S., Jacobsen, S., Jafari, N., Jalosinski, M., Jarius, S., Kapaki, E., Kieseier, B.C., Koel-Simmelink, M.J., Kornhuber, J., Kuhle, J., Kurzepa, J., Lalive, P.H., Lannfelt, L., Lehmensiek, V., Lewczuk, P., Livrea, P., Marnetto, F., Martino, D., Menge, T., Norgren, N., Papuc, E., Paraskevas, G.P., Pirttilä, T., Rajda, C., Rejdak, K., Ricny, J., Ripova, D., Rosengren, L., Ruggieri, M., Schraen, S., Shaw, G., Sindic, C., Siva, A., Stigbrand, T., Stonebridge, I., Topcular, B., Trojano, M., Tumani, H., Twaalfhoven, H.A., Vecsei, L., Pesch, V. Van, Vanderstichele, H., Vedeler, C., Verbeek, M.M., Villar, L.M., Weissert, R., Wildemann, B., Yang, C., Yao, K., Teunissen, C.E., Petzold, A., Altintas, A., Andreoni, L., Bartos, A., Berthele, A., Blankenstein, M.A., Buee, L., Castellazzi, M., Cepok, S., Comabella, M., Constantinescu, C.S., Deisenhammer, F., Deniz, G., Erten, G., Espino, M., Fainardi, E., Franciotta, D., Freedman, M.S., Giedraitis, V., Gilhus, N.E., Giovannoni, G., Glabinski, A., Grieb, P., Hartung, H.P., Hemmer, B., Herukka, S.K., Hintzen, R., Ingelsson, M., Jackson, S., Jacobsen, S., Jafari, N., Jalosinski, M., Jarius, S., Kapaki, E., Kieseier, B.C., Koel-Simmelink, M.J., Kornhuber, J., Kuhle, J., Kurzepa, J., Lalive, P.H., Lannfelt, L., Lehmensiek, V., Lewczuk, P., Livrea, P., Marnetto, F., Martino, D., Menge, T., Norgren, N., Papuc, E., Paraskevas, G.P., Pirttilä, T., Rajda, C., Rejdak, K., Ricny, J., Ripova, D., Rosengren, L., Ruggieri, M., Schraen, S., Shaw, G., Sindic, C., Siva, A., Stigbrand, T., Stonebridge, I., Topcular, B., Trojano, M., Tumani, H., Twaalfhoven, H.A., Vecsei, L., Pesch, V. Van, Vanderstichele, H., Vedeler, C., Verbeek, M.M., Villar, L.M., Weissert, R., Wildemann, B., Yang, C., Yao, K., and Teunissen, C.E.

Abstract

Contains fulltext : 89601.pdf (publisher's version ) (Closed access), BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. RESULTS: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R=0.98, p<0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. CONCLUSION: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.

Published
2010

15. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.

Author

Mattsson, N., Zetterberg, H., Hansson, O., Andreasen, N., Parnetti, L., Jonsson, M., Herukka, S.K., Flier, W.M. van der, Blankenstein, M.A., Ewers, M., Rich, K., Kaiser, E., Verbeek, M.M., Tsolaki, M., Mulugeta, E., Rosen, E., Aarsland, D., Visser, P.J., Schroder, J., Marcusson, J., Leon, M., Hampel, H., Scheltens, P., Pirttilä, T., Wallin, A., Jonhagen, M.E., Minthon, L., Winblad, B., Blennow, K., Mattsson, N., Zetterberg, H., Hansson, O., Andreasen, N., Parnetti, L., Jonsson, M., Herukka, S.K., Flier, W.M. van der, Blankenstein, M.A., Ewers, M., Rich, K., Kaiser, E., Verbeek, M.M., Tsolaki, M., Mulugeta, E., Rosen, E., Aarsland, D., Visser, P.J., Schroder, J., Marcusson, J., Leon, M., Hampel, H., Scheltens, P., Pirttilä, T., Wallin, A., Jonhagen, M.E., Minthon, L., Winblad, B., and Blennow, K.

Abstract

Contains fulltext : 80451.pdf (publisher's version ) (Closed access), CONTEXT: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS: During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau

Published
2009

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