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3. Pre-analytical stability of novel cerebrospinal fluid biomarkers

Author

Willemse, Eline A.J., Vermeiren, Yannick, Garcia-Ayllon, Maria-Salud, Bridel, Claire, De Deyn, Peter P., Engelborghs, Sebastiaan, van der Flier, Wiesje M., Jansen, Erwin E.W., Lopez-Font, Inmaculada B., Mendes, Vera, Manadas, Bruno, de Roeck, Naomi, Saez-Valero, Javier, Struys, Eduard A., Vanmechelen, Eugeen, Andreasson, Ulf, and Teunissen, Charlotte E.

Published
2019
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5. Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project

Author

Willemse, Eline A.J., van Maurik, Ingrid S., Tijms, Betty M., Bouwman, Femke H., Franke, Andreas, Hubeek, Isabelle, Boelaarts, Leo, Claus, Jules J., Korf, Esther S.C., van Marum, Rob J., Roks, Gerwin, Schoonenboom, Niki, Verwey, Nicolaas, Zwan, Marissa D., Wahl, Simone, van der Flier, Wiesje M., and Teunissen, Charlotte E.

Published
2018
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6. Clinical Value of Longitudinal Serum Neurofilament Light Chain in Prodromal Genetic Frontotemporal Dementia

Author

Giannini, Lucia A.A., primary, Seelaar, Harro, additional, van der Ende, Emma L., additional, Poos, Jackie M., additional, Jiskoot, Lize C., additional, Dopper, Elise G.P., additional, Pijnenburg, Yolande A.L., additional, Willemse, Eline A.J., additional, Vermunt, Lisa, additional, Teunissen, Charlotte E., additional, van Swieten, John C., additional, and Meeter, Lieke H., additional

Published
2023
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8. Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design

Author

de Wilde, Arno, van Maurik, Ingrid S., Kunneman, Marleen, Bouwman, Femke, Zwan, Marissa, Willemse, Eline A.J., Biessels, Geert Jan, Minkman, Mirella, Pel, Ruth, Schoonenboom, Niki S.M., Smets, Ellen M.A., Wattjes, Mike P., Barkhof, Frederik, Stephens, Andrew, van Lier, Erik J., Batrla-Utermann, Richard, Scheltens, Philip, Teunissen, Charlotte E., van Berckel, Bart N.M., and van der Flier, Wiesje M.

Published
2017
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10. Serum Glial Fibrillary Acidic Protein compared with Neurofilament Light Chain as Biomarker for Multiple Sclerosis Disease Progression (P5-3.016)

Author

Meier, Stephanie, primary, Benkert, Pascal, additional, Maceski, Aleksandra Maleska, additional, Schaedelin, Sabine, additional, Oechtering, Johanna, additional, Melie-Garcia, Lester, additional, Cagol, Alessandro, additional, Barakovic, Muhamed, additional, Galbusera, Riccardo, additional, Achtnichts, Lutz, additional, Lalive, Patrice H., additional, Bridel, Claire, additional, Müller, Stefanie, additional, Pot, Caroline, additional, Salmen, Anke, additional, Disanto, Giulio, additional, Zecca, Chiara, additional, Abdelhak, Ahmed, additional, Barro, Christian, additional, Thebault, Simon, additional, D’Souza, Marcus, additional, Derfuss, Tobias, additional, Orleth, Annette, additional, Khalil, Michael, additional, Yaldizli, Özguer, additional, Hermesdorf, Marco, additional, Wiendl, Heinz, additional, Piehl, Fredrik, additional, Fischer, Urs, additional, Kappos, Ludwig, additional, Gobbi, Claudio, additional, Granziera, Cristina, additional, Leppert, David, additional, Willemse, Eline A.J., additional, and Kuhle, Jens, additional

Published
2023
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11. Neurofilament Light and Its Association With CNS Involvement in Patients With Classic Infantile Pompe Disease

Author

Mackenbach, Maarten J., Willemse, Eline A.J., van den Dorpel, Jan J.A., van der Beek, Nadine A.M.E., Díaz-Manera, Jordi, Rizopoulos, Dimitris, Teunissen, Charlotte, van der Ploeg, Ans T., van den Hout, Johanna M.P., Mackenbach, Maarten J., Willemse, Eline A.J., van den Dorpel, Jan J.A., van der Beek, Nadine A.M.E., Díaz-Manera, Jordi, Rizopoulos, Dimitris, Teunissen, Charlotte, van der Ploeg, Ans T., and van den Hout, Johanna M.P.

Abstract

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy (ERT) has substantially improved the outcome of classic infantile Pompe disease, an inheritable muscle disease previously fatal at infancy. However, under treatment, patients develop white matter abnormalities and neurocognitive problems. Therefore, upcoming therapies also target the brain. Currently, biomarkers reflecting CNS involvement are lacking. We aimed to study the association of neurofilament light (NfL) and CNS involvement. METHODS: To investigate the potential of NfL, we analyzed serum samples of patients with classic infantile Pompe disease who were treated with ERT. The samples were collected at ages of <1, 5, and 10 years, as well as around MRI scans. We compared the outcomes with levels in age- and sex-matched peers. Control samples were originally collected as part of routine blood work in children who underwent small surgeries and stored in the biobank of the Erasmus MC/Sophia Children's Hospital. RESULTS: We analyzed 74 serum samples of 17 patients collected at ages ranging from 22 days to 21.2 years (1-8 samples per patient) and compared these with outcomes of 71 matched peers. In the first year of age, NfL levels in patients and controls were similar (10.3 vs 11.0 pg/mL), but mixed linear model analysis showed a yearly increase of NfL of 6.0% in patients, compared with a decrease of 8.8% in controls (p < 0.001). Higher NfL was associated with lower IQ scores (p = 0.009) and lower processing speed scores (p = 0.001). DISCUSSION: We found significant differences in NfL levels between patients and controls and a good association between NfL and cognition. NfL deserves further exploration as a biomarker for CNS involvement in patients with classic infantile Pompe disease.

Published
2023

12. Clinical Value of Longitudinal Serum Neurofilament Light Chain in Prodromal Genetic Frontotemporal Dementia

Author

Giannini, Lucia A.A., Seelaar, Harro, van der Ende, Emma L., Poos, Jackie M., Jiskoot, Lize C., Dopper, Elise G.P., Pijnenburg, Yolande A.L., Willemse, Eline A.J., Vermunt, Lisa, Teunissen, Charlotte E., van Swieten, John C., Meeter, Lieke H., Giannini, Lucia A.A., Seelaar, Harro, van der Ende, Emma L., Poos, Jackie M., Jiskoot, Lize C., Dopper, Elise G.P., Pijnenburg, Yolande A.L., Willemse, Eline A.J., Vermunt, Lisa, Teunissen, Charlotte E., van Swieten, John C., and Meeter, Lieke H.

Abstract

BACKGROUND AND OBJECTIVES: Elevated serum neurofilament light chain (NfL) is used to identify carriers of genetic frontotemporal dementia (FTD) pathogenic variants approaching prodromal conversion. Yet, the magnitude and timeline of NfL increase are still unclear. Here, we investigated the predictive and early diagnostic value of longitudinal serum NfL for the prodromal conversion in genetic FTD. METHODS: In a longitudinal observational cohort study of genetic FTD pathogenic variant carriers, we examined the diagnostic accuracy and conversion risk associated with cross-sectional and longitudinal NfL. Time periods relative to prodromal conversion (>3, 3-1.5, 1.5-0 years before; 0-1.5 years after) were compared with values of participants who did not convert. Next, we modeled longitudinal NfL and MRI volume trajectories to determine their timeline.RESULTS: We included 21 participants who converted (5 chromosome 9 open-reading frame 72 [C9orf72], 10 progranulin [GRN], 5 microtubule-associated protein tau [MAPT], and 1 TAR DNA-binding protein [TARDBP]) and 61 who did not (20 C9orf72, 30 GRN, and 11 MAPT). Participants who converted had higher NfL levels at all examined periods before prodromal conversion (median values 14.0-18.2 pg/mL; betas = 0.4-0.7, standard error [SE] = 0.1, p < 0.046) than those who did not (6.5 pg/mL) and showed further increase 0-1.5 years after conversion (28.4 pg/mL; beta = 1.0, SE = 0.1, p < 0.001). Annualized longitudinal NfL change was only significantly higher in participants who converted (vs. participants who did not) 0-1.5 years after conversion (beta = 1.2, SE = 0.3, p = 0.001). Diagnostic accuracy of cross-sectional NfL for prodromal conversion (vs. nonconversion) was good-to-excellent at time periods before conversion (area under the curve range: 0.72-0.92), improved 0-1.5 years after conversion (0.94-0.97), and outperformed annualized longitudinal change (0.76-0.84).

Published
2023

13. Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis

Author

Meier, Stephanie, primary, Willemse, Eline A.J., additional, Schaedelin, Sabine, additional, Oechtering, Johanna, additional, Lorscheider, Johannes, additional, Melie-Garcia, Lester, additional, Cagol, Alessandro, additional, Barakovic, Muhamed, additional, Galbusera, Riccardo, additional, Subramaniam, Suvitha, additional, Barro, Christian, additional, Abdelhak, Ahmed, additional, Thebault, Simon, additional, Achtnichts, Lutz, additional, Lalive, Patrice, additional, Müller, Stefanie, additional, Pot, Caroline, additional, Salmen, Anke, additional, Disanto, Giulio, additional, Zecca, Chiara, additional, D’Souza, Marcus, additional, Orleth, Annette, additional, Khalil, Michael, additional, Buchmann, Arabella, additional, Du Pasquier, Renaud, additional, Yaldizli, Özgür, additional, Derfuss, Tobias, additional, Berger, Klaus, additional, Hermesdorf, Marco, additional, Wiendl, Heinz, additional, Piehl, Fredrik, additional, Battaglini, Marco, additional, Fischer, Urs, additional, Kappos, Ludwig, additional, Gobbi, Claudio, additional, Granziera, Cristina, additional, Bridel, Claire, additional, Leppert, David, additional, Maleska Maceski, Aleksandra, additional, Benkert, Pascal, additional, and Kuhle, Jens, additional

Published
2023
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15. Comparison between plasma, serum and cerebrospinal fluid glial fibrillary acidic protein in Alzheimer’s Disease and Dementia with Lewy bodies and the effect of age and sex on diagnostic performance

Author

Honey, Madison I. J., primary, Wesenhagen, Kirsten E. J., additional, Willemse, Eline A.J., additional, Verberk, Inge M.W., additional, Boonkamp, Lynn, additional, Killestein, Joep, additional, Visser, Pieter Jelle, additional, Tijms, Betty M., additional, and Teunissen, Charlotte E., additional

Published
2022
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17. A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging

Author

Dumurgier, Julien, primary, Sabia, Séverine, additional, Zetterberg, Henrik, additional, Teunissen, Charlotte E., additional, Hanseeuw, Bernard, additional, Orellana, Adelina, additional, Schraen, Susanna, additional, Gabelle, Audrey, additional, Boada, Mercè, additional, Lebouvier, Thibaud, additional, Willemse, Eline A.J., additional, Cognat, Emmanuel, additional, Ruiz, Agustin, additional, Hourregue, Claire, additional, Lilamand, Matthieu, additional, Bouaziz-Amar, Elodie, additional, Laplanche, Jean-Louis, additional, Lehmann, Sylvain, additional, Pasquier, Florence, additional, Scheltens, Philip, additional, Blennow, Kaj, additional, Singh-Manoux, Archana, additional, and Paquet, Claire, additional

Published
2022
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18. A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging

Author

UCL - SSS/IONS/NEUR - Clinical Neuroscience, Dumurgier, Julien, Sabia, Séverine, Zetterberg, Henrik, Teunissen, Charlotte E., Hanseeuw, Bernard, Orellana, Adelina, Schraen, Susanna, Gabelle, Audrey, Boada, Mercè, Lebouvier, Thibaud, Willemse, Eline A.J., Cognat, Emmanuel, Ruiz, Agustin, Hourregue, Claire, Lilamand, Matthieu, Bouaziz-Amar, Elodie, Laplanche, Jean-Louis, Pasquier, Florence, Scheltens, Philip, Blennow, Kaj, Singh-Manoux, Archana, Paquet, Claire, Lehmann, Sylvain, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Dumurgier, Julien, Sabia, Séverine, Zetterberg, Henrik, Teunissen, Charlotte E., Hanseeuw, Bernard, Orellana, Adelina, Schraen, Susanna, Gabelle, Audrey, Boada, Mercè, Lebouvier, Thibaud, Willemse, Eline A.J., Cognat, Emmanuel, Ruiz, Agustin, Hourregue, Claire, Lilamand, Matthieu, Bouaziz-Amar, Elodie, Laplanche, Jean-Louis, Pasquier, Florence, Scheltens, Philip, Blennow, Kaj, Singh-Manoux, Archana, Paquet, Claire, and Lehmann, Sylvain

Abstract

Background and Objectives To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging.

Published
2022

20. A panel of novel astrocytic and synaptic biomarkers in serum and CSF for the differential diagnosis of frontotemporal dementia

Author

Bolsewig, Katharina, primary, Hok‐A‐Hin, Yanaika S., additional, Sepe, Federica Nicoletta, additional, Boonkamp, Lynn, additional, Jacobs, Dirk, additional, Bellomo, Giovanni, additional, Paoletti, Federico Paolini, additional, Vanmechelen, Eugeen, additional, Teunissen, Charlotte E., additional, Parnetti, Lucilla, additional, and Willemse, Eline A.J., additional

Published
2021
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22. Prediction of amyloid PET status using the LUMIPULSE G β‐amyloid ratio (1‐42/1‐40)

Author

Willemse, Eline A.J., primary, Tijms, Betty M., additional, Van Berckel, Bart N.M., additional, van Der Flier, Wiesje, additional, Gannon, Sara, additional, Bastard, Nathalie Le, additional, Radwan, Rachel R., additional, Esquivel, Rianne N., additional, Latham, Jessica, additional, Benina, Natalya, additional, Dickson, Diana, additional, Scheltens, Philip, additional, and Teunissen, Charlotte E., additional

Published
2020
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23. Using cerebrospinal fluid amyloid‐beta (1‐42) in the memory clinic: Concordance with PET and use of biomarker ratios across immunoassays

Author

Willemse, Eline A.J., primary, Tijms, Betty M., additional, Van Berckel, Bart N.M., additional, Gannon, Sara, additional, Le Bastard, Nathalie, additional, Latham, Jessica, additional, Radwan, Rachel R., additional, van Der Flier, Wiesje, additional, Scheltens, Philip, additional, and Teunissen, Charlotte E., additional

Published
2020
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26. Plasma biomarkers of Alzheimer's disease in dementia with Lewy bodies.

Author

Bolsewig, Katharina, Gonzalez, Maria Camila, Ashton, Nicholas J., van Unnik, Annemartijn A. J. M., Blujdea, Elena R., Aarsland, Dag, Zetterberg, Henrik, Padovani, Alessandro, Bonanni, Laura, Mollenhauer, Brit, Schade, Sebastian, Vandenberghe, Rik, Poesen, Koen, Kramberger, Milica G., Paquet, Claire, Bousiges, Olivier, Cretin, Benjamin, Willemse, Eline A.J., Teunissen, Charlotte E., and Lemstra, Afina W.

Abstract

Background: Alzheimer's disease (AD) co‐pathology is a common feature in dementia with Lewy bodies (DLB) and associated with a more rapid decline. Here, we aimed to evaluate plasma biomarkers as alternatives for CSF biomarkers for the detection of amyloid pathology, and for their diagnostic and prognostic value in DLB. Method: Plasma Aβ42/40, GFAP, NfL, pTau181 and pTau231, were measured by SIMOA in patients with DLB (n = 342), AD (n = 131), and healthy controls (n = 89) from the E‐DLB consortium cohort. Associations of biomarkers with CSF Aβ42 status were assessed with ANCOVA corrected for age and sex. ROC analyses were performed to assess biomarker's performance for amyloid detection and differential diagnosis. Associations of biomarkers with cognitive impairment and decline were determined by linear regression and mixed effects models. Result: Altered Aβ42/40 (β = ‐0.0076, 95%CI:‐0.0137 to ‐0.0016, p<.05), pTau181 (β = 0.2503, 95%CI: 0.0555 to 0.4451, p<.05) and pTau231 levels (β = 0.2269, 95%CI:0.0347 to 0.4191, p<.05) were associated with amyloid pathology in DLB, as assessed by CSF Aβ42. The combination of these biomarkers differentiated amyloid normal from abnormal DLB patients with an AUC of 0.728 (sensitivity = 64.6%, specificity = 75.0%). pTau181 best differentiated these groups as a single marker (AUC = 0.700, sensitivity = 62.5%, specificity = 73.1%). The combination of Aβ42/40, NfL and pTau231 differentiated DLB from AD with an AUC of 0.726 (sensitivity = 73.3%, specificity = 68.8%). In DLB, increased GFAP (β = ‐8.9, 95%CI:‐11.7 to ‐6.1, p<.001), NfL (β = ‐7.2, 95%CI:‐10.0 to ‐4.4, p<.001), pTau181 (β = ‐2.6, 95%CI:‐4.0 to ‐1.2, p<.001) and pTau231 (β = ‐2.4, 95%CI:‐3.7 to ‐1.2, p<.001) were associated with lower baseline MMSE scores and increased GFAP (annual change of ‐2.1 MMSE points (95%CI:‐2.9 to ‐1.3, p<.001) and NfL (annual change of ‐2.1 MMSE points (95%CI:‐3.0 to ‐1.3, p<.001) predicted faster cognitive decline. Conclusion: Plasma Aβ42/40, pTau181 and pTau231 were associated with amyloid abnormality in DLB. Their utility for differential diagnosis and identifying amyloid pathology in DLB was modest. Our findings suggest a prognostic value of GFAP and NfL for cognitive decline in DLB. [ABSTRACT FROM AUTHOR]

Published
2023
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27. P4‐270: NEUROGRANIN IN CEREBROSPINAL FLUID IS NOT SPECIFIC TO ALZHEIMER'S DISEASE DEMENTIA

Author

Willemse, Eline A.J., primary, Sieben, Anne, additional, Somers, Charisse, additional, Vermeiren, Yannick, additional, De Roeck, Naomi, additional, Luyckx, Jill, additional, Van Broeckhoven, Christine, additional, De Vil, Bart, additional, Cras, Patrick, additional, De Deyn, Peter Paul, additional, Martin, Jean-Jacques, additional, Teunissen, Charlotte E., additional, Engelborghs, Sebastiaan, additional, and Bjerke, Maria, additional

Published
2018
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28. P2‐228: PRE‐ANALYTICAL STABILITY OF NOVEL CEREBROSPINAL FLUID BIOMARKERS FOR DEMENTIA

Author

Willemse, Eline A.J., primary, Vermeiren, Yannick, additional, García-Ayllón, María-Salud, additional, Bridel, Claire, additional, De Deyn, Peter Paul, additional, Engelborghs, Sebastiaan, additional, Van der Flier, Wiesje M., additional, Janssen, Erwin, additional, Font, Inmaculada Lopes, additional, Manadas, Bruno, additional, Mendes, Vera M., additional, De Roeck, Naomi, additional, Sáez-Valero, Javier, additional, Struys, Eduard A., additional, van Uffelen, Kees WJ., additional, Vanmechelen, Eugeen, additional, Andreasson, Ulf, additional, and Teunissen, Charlotte E., additional

Published
2018
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30. O2‐09‐03: DIAGNOSTIC PERFORMANCE OF ELECSYS IMMUNOASSAYS FOR CEREBROSPINAL FLUID ALZHEIMER'S DISEASE BIOMARKERS IN A NON‐ACADEMIC MULTICENTER MEMORY CLINIC COHORT: THE ABIDE PROJECT

Author

Willemse, Eline A.J., primary, van Maurik, Ingrid S., additional, Tijms, Betty M., additional, Franke, Andreas, additional, Hubeek, Isabelle, additional, Boelaarts, Leo, additional, Claus, Jules J., additional, Korf, Esther S.C., additional, Van Marum, Rob J., additional, Roks, Gerwin, additional, Schoonenboom, Niki S.M., additional, Verwey, Nicolaas, additional, Wahl, Simone, additional, Van der Flier, Wiesje M., additional, and Teunissen, Charlotte E., additional

Published
2018
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32. Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design

Author

Wilde, Arno, primary, Maurik, Ingrid S., additional, Kunneman, Marleen, additional, Bouwman, Femke, additional, Zwan, Marissa, additional, Willemse, Eline A.J., additional, Biessels, Geert Jan, additional, Minkman, Mirella, additional, Pel, Ruth, additional, Schoonenboom, Niki S.M., additional, Smets, Ellen M.A., additional, Wattjes, Mike P., additional, Barkhof, Frederik, additional, Stephens, Andrew, additional, Lier, Erik J., additional, Batrla‐Utermann, Richard, additional, Scheltens, Philip, additional, Teunissen, Charlotte E., additional, Berckel, Bart N.M., additional, and Flier, Wiesje M., additional

Published
2017
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37. DIAGNOSTIC PERFORMANCE OF ELECSYS IMMUNOASSAYS FOR CEREBROSPINAL FLUID ALZHEIMER’S DISEASE BIOMARKERS IN A NON-ACADEMIC MULTICENTER MEMORY CLINIC COHORT: THE ABIDE PROJECT

Author

Willemse, Eline A.J., van Maurik, Ingrid S., Tijms, Betty M., Franke, Andreas, Hubeek, Isabelle, Boelaarts, Leo, Claus, Jules J., Korf, Esther S.C., Van Marum, Rob J., Roks, Gerwin, Schoonenboom, Niki S.M., Verwey, Nicolaas, Wahl, Simone, Van der Flier, Wiesje M., and Teunissen, Charlotte E.

Published
2018
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39. PRE-ANALYTICAL STABILITY OF NOVEL CEREBROSPINAL FLUID BIOMARKERS FOR DEMENTIA

Author

Willemse, Eline A.J., Vermeiren, Yannick, García-Ayllón, María-Salud, Bridel, Claire, De Deyn, Peter Paul, Engelborghs, Sebastiaan, Van der Flier, Wiesje M., Janssen, Erwin, Font, Inmaculada Lopes, Manadas, Bruno, Mendes, Vera M., De Roeck, Naomi, Sáez-Valero, Javier, Struys, Eduard A., van Uffelen, Kees WJ., Vanmechelen, Eugeen, Andreasson, Ulf, and Teunissen, Charlotte E.

Published
2018
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43. Using cerebrospinal fluid amyloid‐beta(1‐42) in the memory clinic: Concordance with PET and use of biomarker ratios across immunoassays: Biomarkers (non‐neuroimaging): Method development and validation.

Author

Willemse, Eline A.J., Tijms, Betty M., Van Berckel, Bart N.M., Gannon, Sara, Le Bastard, Nathalie, Latham, Jessica, Radwan, Rachel R., van Der Flier, Wiesje, Scheltens, Philip, and Teunissen, Charlotte E.

Abstract

Background: Shifting to automated cerebrospinal fluid biomarker platforms urges re‐evaluation of biomarker interpretation in the memory clinic setting. We aimed to evaluate whether different ratios of biomarkers, pTau:Aβ1– 42 and Aβ1– 42:Aβ1– 40, improved the discrimination of amyloid PET positivity in a retrospective cohort and whether this was dependent on the platform used. Method: Cerebrospinal fluid samples of individuals in the biobank of the Amsterdam Dementia Cohort were selected based on availability of visual amyloid PET reads (n=288; n=133 florbetaben, n=86 Pittsburgh compound‐B, n=64 flutemetamol, n=5 florbetapir; 179 (62%) amyloid PET positive; age 63±7 years; 131(45%) female; MMSE 24±4; diagnoses subjective cognitive decline (n=58), mild cognitive impairment (n=42), Alzheimer's disease (AD; n=145), or other dementias (n=43)). Aβ1– 42, Aβ1– 40 (Lumipulse only), pTau and tTau were measured using both Elecsys and Lumipulse automated platforms. Sensitivity and specificity percentages were determined based on optimal Youden's index in receiver operating curve analyses with amyloid PET result as gold standard. Result: Both pTau:Aβ1– 42 and Aβ1– 42:Aβ1– 40 ratios showed higher concordance with amyloid PET compared to Aβ1– 42 alone. Sensitivity and specificity percentages for Elecsys were 96% and 89% for pTau:Aβ1– 42 (cut‐point 0.020), 96% and 80% for Aβ1– 42:Aβ1– 40 (cut‐point 0.091), and 91% and 75% for Aβ1– 42 (cut‐point 1089 pg/ml). For Lumipulse, sensitivity and specificity percentages were 97% and 91% for pTau:Aβ1– 42 (cut‐point 0.072), 99% and 83% for Aβ1– 42:Aβ1– 40 (cut‐point 0.071), 91% and 73% for Aβ1– 42 (cut‐point 714 pg/ml). Areas under the curves were higher for pTau:Aβ1– 42 than Aβ1– 42:Aβ1– 40 using Elecsys (0.949 and 0.924, respectively, p‐value = 0.014) but comparable for both ratios using Lumipulse (0.956 and 0.942, respectively, p‐value = 0.20). Conclusion: We recommend the pTau:Aβ1– 42 ratio as optimal biomarker for use in memory clinic setting using the Elecsys platform, since it showed the strongest concordance with PET amyloid. For Lumipulse assays, pTau:Aβ1– 42 and Aβ1– 42:Aβ1– 40 perform equally well. [ABSTRACT FROM AUTHOR]

Published
2020
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44. Assessing the Pre-Analytical Stability of Small-Molecule Metabolites in Cerebrospinal Fluid Using Direct-Infusion Metabolomics.

Author

Haijes, Hanneke A., Willemse, Eline A.J., Gerrits, Johan, van der Flier, Wiesje M., Teunissen, Charlotte E., Verhoeven-Duif, Nanda M., and Jans, Judith J.M.

Subjects
CEREBROSPINAL fluid, METABOLITES, CEREBROSPINAL fluid examination, METABOLOMICS, MULTIPLE correspondence analysis (Statistics), KRUSKAL-Wallis Test, MASS spectrometry
Abstract

Metabolomics studies aiming to find biomarkers frequently make use of historical or multicenter cohorts. These samples often have different pre-analytical conditions that potentially affect metabolite concentrations. We studied the effect of different storage conditions on the stability of small-molecule metabolites in cerebrospinal fluid to aid a reliable interpretation of metabolomics data. Three cerebrospinal fluid pools were prepared from surplus samples from the Amsterdam Dementia Cohort biobank. Aliquoted pools were exposed to different storage conditions to assess the temperature and freeze/thaw stability before final storage at −80 °C: storage up to four months at −20 °C and up to one week at either 5–8 °C or 18–22 °C and exposure to up to seven freeze/thaw cycles. Direct-infusion high-resolution mass spectrometry was performed, resulting in the identification of 1852 m/z peaks. To test the storage stability, principal component analyses, repeated measures analysis of variance, Kruskal–Wallis tests, and fold change analyses were performed, all demonstrating that small-molecule metabolites in the cerebrospinal fluid (CSF) are relatively unaffected by 1–3 freeze/thaw cycles, by storage at −20 °C up to two months, by storage at 5–8 °C for up to 72 h, or by storage at 18–22 °C for up to 8 h. This suggests that these differences do not affect the interpretation of potential small-molecule biomarkers in multicenter or historical cohorts and implies that these cohorts are suitable for biomarker studies. [ABSTRACT FROM AUTHOR]

Published
2019
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