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1. Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology

Author

Blömeke, Lara, primary, Rehn, Fabian, additional, Kraemer‐Schulien, Victoria, additional, Kutzsche, Janine, additional, Pils, Marlene, additional, Bujnicki, Tuyen, additional, Lewczuk, Piotr, additional, Kornhuber, Johannes, additional, Freiesleben, Silka D., additional, Schneider, Luisa‐Sophie, additional, Preis, Lukas, additional, Priller, Josef, additional, Spruth, Eike J., additional, Altenstein, Slawek, additional, Lohse, Andrea, additional, Schneider, Anja, additional, Fliessbach, Klaus, additional, Wiltfang, Jens, additional, Hansen, Niels, additional, Rostamzadeh, Ayda, additional, Düzel, Emrah, additional, Glanz, Wenzel, additional, Incesoy, Enise I., additional, Butryn, Michaela, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Ewers, Michael, additional, Perneczky, Robert, additional, Rauchmann, Boris‐Stephan, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Goerss, Doreen, additional, Laske, Christoph, additional, Munk, Matthias H., additional, Sanzenbacher, Carolin, additional, Spottke, Annika, additional, Roy‐Kluth, Nina, additional, Heneka, Michael T., additional, Brosseron, Frederic, additional, Wagner, Michael, additional, Wolfsgruber, Steffen, additional, Kleineidam, Luca, additional, Stark, Melina, additional, Schmid, Matthias, additional, Jessen, Frank, additional, Bannach, Oliver, additional, Willbold, Dieter, additional, and Peters, Oliver, additional

Published
2024
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2. Altered BOLD Signal Fluctuations in precuneus relate to inflammatory markers and vascular risk in the AD spectrum

Author

Maass, Anne, primary, Behrenbruch, Niklas, additional, Incesoy, Enise I, additional, Brosseron, Frederic, additional, Menze, Inga, additional, Bernal, Jose, additional, Hayek, Dayana, additional, Kleineidam, Luca, additional, Bürger, Katharina, additional, Fliessbach, Klaus, additional, Laske, Christoph, additional, Perneczky, Robert, additional, Peters, Oliver, additional, Priller, Josef, additional, Schneider, Anja, additional, Spottke, Annika, additional, Teipel, Stefan, additional, Wiltfang, Jens, additional, Wolfsgruber, Steffen, additional, Yakupov, Renat, additional, Wagner, Michael, additional, Jessen, Frank, additional, Duzel, Emrah, additional, Schreiber, Stefanie, additional, Heneka, Michael T., additional, and Ziegler, Gabriel, additional

Published
2023
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3. Locus coeruleus MRI contrast is associated with Complement factor C3b in cerebrospinal fluid

Author

Neumann, Laura, primary, Hayek, Dayana, additional, Sarkar, Mousumi, additional, Heinzinger, Nils, additional, Hämmerer, Dorothea, additional, Schneider, Anja, additional, Fließbach, Klaus, additional, Teipel, Stefan, additional, Spottke, Annika, additional, Brosseron, Frederic, additional, Jessen, Frank, additional, Düzel, Emrah, additional, Heneka, Michael T., additional, Maass, Anne, additional, and Betts, Matthew, additional

Published
2023
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4. Machine learning‐based classification of Alzheimer's disease and its at‐risk states using personality traits, anxiety, and depression

Author

Waschkies, Konrad F., primary, Soch, Joram, additional, Darna, Margarita, additional, Richter, Anni, additional, Altenstein, Slawek, additional, Beyle, Aline, additional, Brosseron, Frederic, additional, Buchholz, Friederike, additional, Butryn, Michaela, additional, Dobisch, Laura, additional, Ewers, Michael, additional, Fliessbach, Klaus, additional, Gabelin, Tatjana, additional, Glanz, Wenzel, additional, Goerss, Doreen, additional, Gref, Daria, additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Lohse, Andrea, additional, Munk, Matthias H., additional, Rauchmann, Boris‐Stephan, additional, Rostamzadeh, Ayda, additional, Roy, Nina, additional, Spruth, Eike Jakob, additional, Dechent, Peter, additional, Heneka, Michael T., additional, Hetzer, Stefan, additional, Ramirez, Alfredo, additional, Scheffler, Klaus, additional, Buerger, Katharina, additional, Laske, Christoph, additional, Perneczky, Robert, additional, Peters, Oliver, additional, Priller, Josef, additional, Schneider, Anja, additional, Spottke, Annika, additional, Teipel, Stefan, additional, Düzel, Emrah, additional, Jessen, Frank, additional, Wiltfang, Jens, additional, Schott, Björn H., additional, and Kizilirmak, Jasmin M., additional

Published
2023
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5. A Cognitive Reserve Network That Moderates the Relationship Between Alzheimer’s Disease Pathology and Cognition

Author

Vockert, Niklas, primary, Schütze, Hartmut, additional, Richter, Anni, additional, Altenstein, Slawek, additional, Bartels, Claudia, additional, Brosseron, Frederic, additional, Cardenas‐Blanco, Arturo, additional, Dahmen, Philip, additional, Dechent, Peter, additional, Dobisch, Laura, additional, Fließbach, Klaus, additional, Freiesleben, Silka Dawn, additional, Glanz, Wenzel, additional, Goerss, Doreen, additional, Haynes, John‐Dylan, additional, Heneka, Michael T., additional, Kilimann, Ingo, additional, Kimmich, Okka, additional, Kleineidam, Luca, additional, Laske, Christoph, additional, Lohse, Andrea, additional, Metzger, Coraline D., additional, Munk, Matthias H. J., additional, Peters, Oliver, additional, Preis, Lukas, additional, Priller, Josef, additional, Ramirez, Alfredo, additional, Roeske, Sandra, additional, Rostamzadeh, Ayda, additional, Roy, Nina, additional, Scheffler, Klaus, additional, Schneider, Anja, additional, Spottke, Annika, additional, Spruth, Eike Jakob, additional, Teipel, Stefan, additional, Wagner, Michael, additional, Wiltfang, Jens, additional, Wolfsgruber, Steffen, additional, Yakupov, Renat, additional, Zeidman, Peter, additional, Jessen, Frank, additional, Schott, Björn H, additional, Duzel, Emrah, additional, Maass, Anne, additional, and Ziegler, Gabriel, additional

Published
2022
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6. Soluble TAM receptor biomarkers: Neuroprotection in AD neuroinflammation?"

Author

Brosseron, Frederic, primary, Maass, Anne, additional, Kleineidam, Luca, additional, Ravichandran, Kishore Aravind, additional, Peters, Oliver, additional, Priller, Josef, additional, Schneider, Anja, additional, Fließbach, Klaus, additional, Wiltfang, Jens, additional, Duzel, Emrah, additional, Buerger, Katharina, additional, Perneczky, Robert, additional, Teipel, Stefan, additional, Laske, Christoph, additional, Spottke, Annika, additional, Teunissen, Charlotte E., additional, Synofzik, Matthis, additional, Wagner, Michael, additional, Jessen, Frank, additional, Ramirez, Alfredo, additional, Ruiz, Agustin, additional, and Heneka, Michael T., additional

Published
2022
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7. Speed of cognitive decline in biomarker stratified SCD subgroups

Author

Jessen, Frank, primary, Kleineidam, Luca, additional, Wolfsgruber, Steffen, additional, Spottke, Annika, additional, Brosseron, Frederic, additional, Laske, Christoph, additional, Perneczky, Robert, additional, Schneider, Anja, additional, Wiltfang, Jens, additional, Teipel, Stefan, additional, Bürger, Katharina, additional, Priller, Josef, additional, Peters, Oliver, additional, Ramirez, Alfredo, additional, Boecker, Henning, additional, Heneka, Michael T., additional, Wagner, Michael, additional, and Duzel, Emrah, additional

Published
2022
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8. Reactive microglia are the major source of tumor necrosis factor alpha and contribute to astrocyte dysfunction and acute seizures in experimental temporal lobe epilepsy

Author

Henning, Lukas, primary, Antony, Henrike, additional, Breuer, Annika, additional, Müller, Julia, additional, Seifert, Gerald, additional, Audinat, Etienne, additional, Singh, Parmveer, additional, Brosseron, Frederic, additional, Heneka, Michael T., additional, Steinhäuser, Christian, additional, and Bedner, Peter, additional

Published
2022
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9. Subjective cognitive decline and stage 2 of Alzheimer disease in patients from memory centers

Author

Jessen, Frank, primary, Wolfsgruber, Steffen, additional, Kleineindam, Luca, additional, Spottke, Annika, additional, Altenstein, Slawek, additional, Bartels, Claudia, additional, Berger, Moritz, additional, Brosseron, Frederic, additional, Daamen, Marcel, additional, Dichgans, Martin, additional, Dobisch, Laura, additional, Ewers, Michael, additional, Fenski, Friederike, additional, Fliessbach, Klaus, additional, Freiesleben, Silka D., additional, Glanz, Wenzel, additional, Görß, Doreen, additional, Gürsel, Selim, additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Kobeleva, Xenia, additional, Lohse, Andrea, additional, Maier, Franziska, additional, Metzger, Coraline, additional, Munk, Matthias, additional, Preis, Lukas, additional, Sanzenbacher, Carolin, additional, Spruth, Eike, additional, Rauchmann, Boris, additional, Vukovich, Ruth, additional, Yakupov, Renat, additional, Weyrauch, Anne‐Sophie, additional, Ziegler, Gabriel, additional, Schmid, Matthias, additional, Laske, Christoph, additional, Perneczky, Robert, additional, Schneider, Anja, additional, Wiltfang, Jens, additional, Teipel, Stefan, additional, Bürger, Katharina, additional, Priller, Josef, additional, Peters, Oliver, additional, Ramirez, Alfredo, additional, Boecker, Henning, additional, Heneka, Michael T., additional, Wagner, Michael, additional, and Düzel, Emrah, additional

Published
2022
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10. Individualized MR‐based prediction of cognitive performance in subjects at risk of dementia

Author

Nemali, Aditya Sai Ram, primary, Yakupov, Renat, additional, Schütze, Hartmut, additional, Spottke, Annika, additional, Ramirez, Alfredo, additional, Schneider, Anja, additional, Metzger, Coraline D., additional, Christoph, Laske, additional, Bittner, Daniel, additional, Brosseron, Frederic, additional, Priller, Josef, additional, Wiltfang, Jens, additional, Buerger, Katharina, additional, Fließbach, Klaus, additional, Heneka, Michael T., additional, Peters, Oliver, additional, Speck, Oliver, additional, Nestor, Peter J., additional, Teipel, Stefan J., additional, Pross, Verena, additional, Glanz, Wenzel, additional, Wagner, Michael, additional, Jessen, Frank, additional, Düzel, Emrah, additional, and Ziegler, Gabriel, additional

Published
2021
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11. Exploring the ATN classification system using brain morphology

Author

Heinzinger, Nils, primary, Maass, Anne, additional, Yakupov, Renat, additional, Schütze, Hartmut, additional, Spottke, Annika, additional, Ramirez, Alfredo, additional, Schneider, Anja, additional, Metzger, Coraline D., additional, Laske, Christoph, additional, Bittner, Daniel, additional, Brosseron, Frederic, additional, Priller, Josef, additional, Wiltfang, Jens, additional, Buerger, Katharina, additional, Fließbach, Klaus, additional, Heneka, Michael T., additional, Peters, Oliver, additional, Speck, Oliver, additional, Nestor, Peter J., additional, Teipel, Stefan J., additional, Pross, Verena, additional, Glanz, Wenzel, additional, Wagner, Michael, additional, Jessen, Frank, additional, Düzel, Emrah, additional, and Ziegler, Gabriel, additional

Published
2021
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12. Multi‐cohort profiling reveals elevated CSF levels of brain‐enriched proteins in Alzheimer’s disease

Author

Bergström, Sofia, primary, Remnestål, Julia, additional, Yousef, Jamil, additional, Olofsson, Jennie, additional, Markaki, Ioanna, additional, Carvalho, Stephanie, additional, Corvol, Jean‐Christophe, additional, Kultima, Kim, additional, Kilander, Lena, additional, Löwenmark, Malin, additional, Ingelsson, Martin, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, Nellgård, Bengt, additional, Brosseron, Frederic, additional, Heneka, Michael T., additional, Bosch, Beatriz, additional, Sanchez‐Valle, Raquel, additional, Månberg, Anna, additional, Svenningsson, Per, additional, and Nilsson, Peter, additional

Published
2021
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13. A microRNA signature that correlates with cognition and is a target against cognitive decline

Author

Islam, Md Rezaul, Kaurani, Lalit, Berulava, Tea, Heilbronner, Urs, Budde, Monika, Centeno, Tonatiuh Pena, Elerdashvili, Vakthang, Zafieriou, Maria-Patapia, Benito, Eva, Sertel, Sinem M., Goldberg, Maria, Senner, Fanny, Kalman, Janos L., Burkhardt, Susanne, Oepen, Anne Sophie, Sakib, Mohammad Sadman, Kerimolgu, Cemil, Wirths, Oliver, Bickeboeller, Heike, Bartels, Claudia, Brosseron, Frederic, Buerger, Katharina, Cosma, Nicoleta-Carmen, Fliessbach, Klaus, Heneka, Michael T., Janowitz, Daniel, Kilimann, Ingo, Kleinedam, Luca, Laske, Christoph, Metzger, Coraline D., Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris S., Roy, Nina, Schneider, Anja, Spottke, Annika, Spruth, Eike J., Teipel, Stefan, Tscheuschler, Maike, Wagner, Michael, Wiltfang, Jens, Duzel, Emrah, Jessen, Frank, Rizzoli, Silvio O., Zimmermann, Wolfram-Hubertus, Schulze, Thomas G., Falkai, Peter, Sananbenesi, Farahnaz, Fischer, Andre, Islam, Md Rezaul, Kaurani, Lalit, Berulava, Tea, Heilbronner, Urs, Budde, Monika, Centeno, Tonatiuh Pena, Elerdashvili, Vakthang, Zafieriou, Maria-Patapia, Benito, Eva, Sertel, Sinem M., Goldberg, Maria, Senner, Fanny, Kalman, Janos L., Burkhardt, Susanne, Oepen, Anne Sophie, Sakib, Mohammad Sadman, Kerimolgu, Cemil, Wirths, Oliver, Bickeboeller, Heike, Bartels, Claudia, Brosseron, Frederic, Buerger, Katharina, Cosma, Nicoleta-Carmen, Fliessbach, Klaus, Heneka, Michael T., Janowitz, Daniel, Kilimann, Ingo, Kleinedam, Luca, Laske, Christoph, Metzger, Coraline D., Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris S., Roy, Nina, Schneider, Anja, Spottke, Annika, Spruth, Eike J., Teipel, Stefan, Tscheuschler, Maike, Wagner, Michael, Wiltfang, Jens, Duzel, Emrah, Jessen, Frank, Rizzoli, Silvio O., Zimmermann, Wolfram-Hubertus, Schulze, Thomas G., Falkai, Peter, Sananbenesi, Farahnaz, and Fischer, Andre

Abstract

While some individuals age without pathological memory impairments, others develop age-associated cognitive diseases. Since changes in cognitive function develop slowly over time in these patients, they are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for the identification of inexpensive and minimal invasive approaches that could be used for screening with the aim to identify individuals at risk for cognitive decline that can then undergo further diagnostics and eventually stratified therapies. In this study, we use an integrative approach combining the analysis of human data and mechanistic studies in model systems to identify a circulating 3-microRNA signature that reflects key processes linked to neural homeostasis and inform about cognitive status. We furthermore provide evidence that expression changes in this signature represent multiple mechanisms deregulated in the aging and diseased brain and are a suitable target for RNA therapeutics.

Published
2021

14. Multi‐cohort profiling reveals elevated CSF levels of brain‐enriched proteins in Alzheimer’s disease

Author

Bergström, Sofia, Remnestål, Julia, Yousef, Jamil, Olofsson, Jennie, Markaki, Ioanna, Carvalho, Stephanie, Corvol, Jean‐Christophe, Kultima, Kim, Kilander, Lena, Löwenmark, Malin, Ingelsson, Martin, Blennow, Kaj, Zetterberg, Henrik, Nellgård, Bengt, Brosseron, Frederic, Heneka, Michael T., Bosch, Beatriz, Sanchez‐Valle, Raquel, Månberg, Anna, Svenningsson, Per, Nilsson, Peter, Bergström, Sofia, Remnestål, Julia, Yousef, Jamil, Olofsson, Jennie, Markaki, Ioanna, Carvalho, Stephanie, Corvol, Jean‐Christophe, Kultima, Kim, Kilander, Lena, Löwenmark, Malin, Ingelsson, Martin, Blennow, Kaj, Zetterberg, Henrik, Nellgård, Bengt, Brosseron, Frederic, Heneka, Michael T., Bosch, Beatriz, Sanchez‐Valle, Raquel, Månberg, Anna, Svenningsson, Per, and Nilsson, Peter

Abstract

Objective: Decreased amyloid beta (Ab) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer’s disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. Methods: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. Results: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of Ab42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. Interpretation: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum., QC 20211116

Published
2021
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15. Interrelations of Alzheimer´s disease candidate biomarkers neurogranin, fatty acid‐binding protein 3 and ferritin to neurodegeneration and neuroinflammation

Author

Brosseron, Frederic, Kleemann, Kilian, Kolbe, Carl‐Christian, Santarelli, Francesco, Castro‐Gomez, Sergio, Tacik, Pawel, Latz, Eicke, Jessen, Frank, Heneka, Michael T., Brosseron, Frederic, Kleemann, Kilian, Kolbe, Carl‐Christian, Santarelli, Francesco, Castro‐Gomez, Sergio, Tacik, Pawel, Latz, Eicke, Jessen, Frank, and Heneka, Michael T.

Published
2021

16. Hippocampal volumetric variability is associated with memory in subjective cognitive decline

Author

Ziegler, Gabriel, primary, Heinzinger, Nils, additional, Metzger, Coraline D., additional, Yakupov, Renat, additional, Bittner, Daniel, additional, Glanz, Wenzel, additional, Spottke, Annika, additional, Brosseron, Frederic, additional, Bürger, Katharina, additional, Fließbach, Klaus, additional, Heneka, Michael T., additional, Laske, Christoph, additional, Nestor, Peter J., additional, Peters, Oliver, additional, Priller, Josef, additional, Ramirez, Alfredo, additional, Schneider, Anja, additional, Speck, Oliver, additional, Teipel, Stefan J., additional, Wiltfang, Jens, additional, Wagner, Michael, additional, Düzel, Emrah, additional, and Jessen, Frank, additional

Published
2020
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17. Innate immune activation of the NLRP3 inflammasome pathway drives tau pathology

Author

Ising, Christina, primary, Venegas, Carmen, additional, Zhang, Shuangshuang, additional, Scheiblich, Hannah, additional, Schmidt, Susanne V., additional, Vieira‐Saecker, Ana, additional, Schwartz, Stephanie, additional, Albasset, Shadi, additional, McManus, Roisin M., additional, Tejera, Dario, additional, Griep, Angelika, additional, Santarelli, Francesco, additional, Brosseron, Frederic, additional, Opitz, Sabine, additional, Stunden, James, additional, Kayed, Rakez, additional, Golenbock, Douglas T., additional, Blum, David, additional, Latz, Eicke, additional, Buee, Luc, additional, and Heneka, Michael T., additional

Published
2020
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20. Memorability of photographs in subjective cognitive decline and mild cognitive impairment: Implications for cognitive assessment

Author

Bainbridge, Wilma A., primary, Berron, David, additional, Schütze, Hartmut, additional, Cardenas‐Blanco, Arturo, additional, Metzger, Coraline, additional, Dobisch, Laura, additional, Bittner, Daniel, additional, Glanz, Wenzel, additional, Spottke, Annika, additional, Rudolph, Janna, additional, Brosseron, Frederic, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Fliessbach, Klaus, additional, Heneka, Michael, additional, Laske, Christoph, additional, Buchmann, Martina, additional, Peters, Oliver, additional, Diesing, Dominik, additional, Li, Siyao, additional, Priller, Josef, additional, Spruth, Eike Jakob, additional, Altenstein, Slawek, additional, Schneider, Anja, additional, Kofler, Barbara, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Wiltfang, Jens, additional, Bartels, Claudia, additional, Wolfsgruber, Steffen, additional, Wagner, Michael, additional, Jessen, Frank, additional, Baker, Chris I., additional, and Düzel, Emrah, additional

Published
2019
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22. P2‐431: RELATIONSHIP BETWEEN LOCAL RESTING STATE ACTIVITY, β‐AMYLOID DEPOSITION AND MEMORY PERFORMANCE IN THE DZNE: LONGITUDINAL COGNITIVE IMPAIRMENT AND DEMENTIA STUDY (DELCODE)

Author

Metzger, Coraline D., primary, Dyrba, Martin, additional, Bittner, Daniel, additional, Hu, Xiaochen, additional, Jessen, Frank, additional, Teipel, Stefan J., additional, Grothe, Michael, additional, Oliver, Peters, additional, Menne, Felix, additional, Fuentes, Manuel, additional, Priller, Josef, additional, Spruth, Eike, additional, Franke, Christiana, additional, Schneider, Anja, additional, Fließbach, Klaus, additional, Kofler, Barbara, additional, Wiltfang, Jens, additional, Bartels, Claudia, additional, Buerger, Katharina, additional, Catak, Cihan, additional, Kilimann, Ingo, additional, Henf, Judith, additional, Laske, Christoph, additional, Buchmann, Martina, additional, Spottke, Annika, additional, Thelen, Manuela, additional, Heneka, Michael T., additional, Brosseron, Frederic, additional, Ramirez, Alfredo, additional, Wagner, Michael, additional, Wolfsgruber, Steffen, additional, Roeske, Sandra, additional, Frommann, Ingo, additional, Polcher, Alexandra, additional, Dobisch, Laura, additional, and Düzel, Emrah, additional

Published
2018
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23. CSF total tau levels are associated with hippocampal novelty irrespective of hippocampal volume

Author

Düzel, Emrah, primary, Berron, David, additional, Schütze, Hartmut, additional, Cardenas‐Blanco, Arturo, additional, Metzger, Coraline, additional, Betts, Matthew, additional, Ziegler, Gabriel, additional, Chen, Yi, additional, Dobisch, Laura, additional, Bittner, Daniel, additional, Glanz, Wenzel, additional, Reuter, Martin, additional, Spottke, Annika, additional, Rudolph, Janna, additional, Brosseron, Frederic, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Fliessbach, Klaus, additional, Heneka, Michael, additional, Laske, Christoph, additional, Buchmann, Martina, additional, Nestor, Peter, additional, Peters, Oliver, additional, Diesing, Dominik, additional, Li, Siyao, additional, Priller, Josef, additional, Spruth, Eike Jakob, additional, Altenstein, Slawek, additional, Ramirez, Alfredo, additional, Schneider, Anja, additional, Kofler, Barbara, additional, Speck, Oliver, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Dyrba, Martin, additional, Wiltfang, Jens, additional, Bartels, Claudia, additional, Wolfsgruber, Steffen, additional, Wagner, Michael, additional, and Jessen, Frank, additional

Published
2018
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29. Interrelations of Alzheimer ' s disease candidate biomarkers neurogranin, fatty acid-binding protein 3 and ferritin to neurodegeneration and neuroinflammation

Author

Brosseron, Frederic, Kleemann, Kilian, Kolbe, Carl-Christian, Santarelli, Francesco, Castro-Gomez, Sergio, Tacik, Pawel, Latz, Eicke, Jessen, Frank, Heneka, Michael T., Brosseron, Frederic, Kleemann, Kilian, Kolbe, Carl-Christian, Santarelli, Francesco, Castro-Gomez, Sergio, Tacik, Pawel, Latz, Eicke, Jessen, Frank, and Heneka, Michael T.

Abstract

There is growing evidence that promising biomarkers of inflammation in Alzheimer ' s disease (AD) and other neurodegenerative diseases correlate strongest to levels of tau or neurofilament, indicating an inflammatory response to neuronal damage or death. To test this hypothesis, we investigated three AD candidate markers (ferritin, fatty acid binding protein 3 (FABP-3), and neurogranin) in interrelation to established AD and inflammatory protein markers. We further aimed to determine if such interrelations would be evident in pathological subjects only or also under non-pathological circumstances. Cerebrospinal fluid levels of the three proteins were quantified in samples from the University Clinic of Bonn (UKB) Department of Neurodegenerative Diseases & Geriatric Psychiatry, Germany. Data were analyzed based on clinical or biomarker-defined stratification of subjects with adjustment for covariates age, sex, andAPOEstatus. Levels of ferritin, FABP-3 and neurogranin were elevated in subjects with pathological levels of t-tau independent of beta-amyloid status. The three markers correlated with each other, tau isoforms, age, and those inflammatory markers previously described as related to neurodegeneration, predominantly sTREM2, macrophage migration inhibitory factor, soluble vascular endothelial growth factor receptor, soluble vascular cell adhesion molecule 1 (sVCAM-1), and C1q. These interrelations existed in subjects with pathological and sub-pathological tau levels, in particular for FABP-3 and neurogranin. Relations to ferritin were independent of absolute levels of tau, too, but showed differing trajectories between pathological and non-pathological subjects. A specific set of inflammatory markers is highly related to markers of neuronal damage such as tau, neurogranin, or FABP-3. These proteins could be used as readouts of the inflammatory response during the neurodegeneration phase of AD.

30. Subjective cognitive decline and stage 2 of Alzheimer disease in patients from memory centers

Author

Jessen, Frank, Wolfsgruber, Steffen, Kleineindam, Luca, Spottke, Annika, Altenstein, Slawek, Bartels, Claudia, Berger, Moritz, Brosseron, Frederic, Daamen, Marcel, Dichgans, Martin, Dobisch, Laura, Ewers, Michael, Fenski, Friederike, Fliessbach, Klaus, Freiesleben, Silka D., Glanz, Wenzel, Goerss, Doreen, Guersel, Selim, Janowitz, Daniel, Kilimann, Ingo, Kobeleva, Xenia, Lohse, Andrea, Maier, Franziska, Metzger, Coraline, Munk, Matthias, Preis, Lukas, Sanzenbacher, Carolin, Spruth, Eike, Rauchmann, Boris, Vukovich, Ruth, Yakupov, Renat, Weyrauch, Anne-Sophie, Ziegler, Gabriel, Schmid, Matthias, Laske, Christoph, Perneczky, Robert, Schneider, Anja, Wiltfang, Jens, Teipel, Stefan, Buerger, Katharina, Priller, Josef, Peters, Oliver, Ramirez, Alfredo, Boecker, Henning, Heneka, Michael T., Wagner, Michael, Duezel, Emrah, Jessen, Frank, Wolfsgruber, Steffen, Kleineindam, Luca, Spottke, Annika, Altenstein, Slawek, Bartels, Claudia, Berger, Moritz, Brosseron, Frederic, Daamen, Marcel, Dichgans, Martin, Dobisch, Laura, Ewers, Michael, Fenski, Friederike, Fliessbach, Klaus, Freiesleben, Silka D., Glanz, Wenzel, Goerss, Doreen, Guersel, Selim, Janowitz, Daniel, Kilimann, Ingo, Kobeleva, Xenia, Lohse, Andrea, Maier, Franziska, Metzger, Coraline, Munk, Matthias, Preis, Lukas, Sanzenbacher, Carolin, Spruth, Eike, Rauchmann, Boris, Vukovich, Ruth, Yakupov, Renat, Weyrauch, Anne-Sophie, Ziegler, Gabriel, Schmid, Matthias, Laske, Christoph, Perneczky, Robert, Schneider, Anja, Wiltfang, Jens, Teipel, Stefan, Buerger, Katharina, Priller, Josef, Peters, Oliver, Ramirez, Alfredo, Boecker, Henning, Heneka, Michael T., Wagner, Michael, and Duezel, Emrah

Abstract

Introduction It is uncertain whether subjective cognitive decline (SCD) in individuals who seek medical help serves the identification of the initial symptomatic stage 2 of the Alzheimer's disease (AD) continuum. Methods Cross-sectional and longitudinal data from the multicenter, memory clinic-based DELCODE study. Results The SCD group showed slightly worse cognition as well as more subtle functional and behavioral symptoms than the control group (CO). SCD-A+ cases (39.3% of all SCD) showed greater hippocampal atrophy, lower cognitive and functional performance, and more behavioral symptoms than CO-A+. Amyloid concentration in the CSF had a greater effect on longitudinal cognitive decline in SCD than in the CO group. Discussion Our data suggests that SCD serves the identification of stage 2 of the AD continuum and that stage 2, operationalized as SCD-A+, is associated with subtle, but extended impact of AD pathology in terms of neurodegeneration, symptoms and clinical progression.

31. Interrelations of Alzheimer ' s disease candidate biomarkers neurogranin, fatty acid-binding protein 3 and ferritin to neurodegeneration and neuroinflammation

Author

Brosseron, Frederic, Kleemann, Kilian, Kolbe, Carl-Christian, Santarelli, Francesco, Castro-Gomez, Sergio, Tacik, Pawel, Latz, Eicke, Jessen, Frank, Heneka, Michael T., Brosseron, Frederic, Kleemann, Kilian, Kolbe, Carl-Christian, Santarelli, Francesco, Castro-Gomez, Sergio, Tacik, Pawel, Latz, Eicke, Jessen, Frank, and Heneka, Michael T.

Abstract

There is growing evidence that promising biomarkers of inflammation in Alzheimer ' s disease (AD) and other neurodegenerative diseases correlate strongest to levels of tau or neurofilament, indicating an inflammatory response to neuronal damage or death. To test this hypothesis, we investigated three AD candidate markers (ferritin, fatty acid binding protein 3 (FABP-3), and neurogranin) in interrelation to established AD and inflammatory protein markers. We further aimed to determine if such interrelations would be evident in pathological subjects only or also under non-pathological circumstances. Cerebrospinal fluid levels of the three proteins were quantified in samples from the University Clinic of Bonn (UKB) Department of Neurodegenerative Diseases & Geriatric Psychiatry, Germany. Data were analyzed based on clinical or biomarker-defined stratification of subjects with adjustment for covariates age, sex, andAPOEstatus. Levels of ferritin, FABP-3 and neurogranin were elevated in subjects with pathological levels of t-tau independent of beta-amyloid status. The three markers correlated with each other, tau isoforms, age, and those inflammatory markers previously described as related to neurodegeneration, predominantly sTREM2, macrophage migration inhibitory factor, soluble vascular endothelial growth factor receptor, soluble vascular cell adhesion molecule 1 (sVCAM-1), and C1q. These interrelations existed in subjects with pathological and sub-pathological tau levels, in particular for FABP-3 and neurogranin. Relations to ferritin were independent of absolute levels of tau, too, but showed differing trajectories between pathological and non-pathological subjects. A specific set of inflammatory markers is highly related to markers of neuronal damage such as tau, neurogranin, or FABP-3. These proteins could be used as readouts of the inflammatory response during the neurodegeneration phase of AD.

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