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Alzheimer′s Disease

Alzheimer´s disease (AD) is a progressive, neurodegenerative disorder, which is characterized by progressive memory deficits, cognitive impairments and personality changes. AD is the most common type of dementia (60%). Currently more than 24 million people are affected worldwide. It is estimated that this number will almost be doubled to 44 million by 2030. Age is the most important risk factor for AD. In the age group of 65 to 69, every 20th person suffers from dementia, but in the age group of 80 to 90 already every fourth person is affected.  In addition to the immense distress of the patients and their families, the total estimated costs of AD are about US$ 600 billion with strongly increasing tendency, making it a major thread for our healthcare systems. 

So far there is no causal therapy for AD. Currently only two medicinal products, i.e. acetylcholinesterase inhibitors and the NMDA receptor antagonist Memantin, are available, which only temporarily improve symptoms, but are not able to slow down, halt or even reverse disease progression. Due to this fact, researchers worldwide are currently working hard towards effective drugs.


A pathological hallmark of Alzheimer's disease is the deposition of amyloid plaques, which are present long before onset of clinical symptoms. Plaques consist mainly of amyloid-ß-peptides (Aβ). Aß is produced from the amyloid precursor protein (APP) by distinct proteolytic activities, called β- and γ-secretases. The resulting Aß monomers are not toxic per se, but they can form small soluble aggregates (oligomers) and amyloid fibrils. It is generally assumed that diffusible Aβ oligomers are the major toxic species responsible for disease development and progression.

Up to now, efforts have concentrated to reduce generation of Aß or reduce its concentration in order to decrease Aß aggregation. In our opinion, instead of Aß monomers the Aß oligomers should be the target of any treatment. Thus, we focus on the development drugs that are able to destroy toxic Aß oligomers. Additionally, Aß oligomers or aggregates could be exploited as early biomarkers for AD, which are urgently needed for measuring therapeutic effects of drug candidates.

The Bannach group is developing an ultra-sensitive and quantitative method for early and pre-symptomatic diagnosis of AD, via detection and quantitation of Aß aggregates in liquor and blood.

The Kutzsche group is pursuing and developing new therapeutic approaches for the treatment of AD.



  • Abyzov A, Mandelkow E, Zweckstetter M, Rezaei-Ghaleh N 
    Fast Motions Dominate Dynamics of Intrinsically Disordered Tau Protein at High Temperatures 
    Chem Eur J 29, e202203493 (2023) 
  • Altendorf T, Gering I, Santiago-Schübel B, Aghabashlou Saisan S, Tamgüney G, Tusche M, Honold D, Schemmert S, Hoyer W, Mohrlüder J, Willbold D 
    Stabilization of monomeric Tau protein by all D-enantiomeric peptide ligands as therapeutic strategy for Alzheimer's disease and other tauopathies 
    Int J Mol Sci 24, 2161 (2023) 
  • Becker C, Giller K, Sieme D, Rezaei-Ghaleh N 
    Maturation of amyloid ß fibrils alters their molecular stability 
    Phys Chem Chem Phys 25, 15099 - 15103 (2023) 
  • Kutzsche J, Schemmert S, Bujnicki T, Zafiu C, Halbgebauer S, Kraemer-Schulien V, Pils M, Blömeke L, Post J, Kulawik A, Jürgens D, Rossberg WM, Hümpel M, Bannach O, Otto M, Araujo JA, Willuweit A, Willbold D. 
    Oral treatment with the all-d-peptide RD2 enhances cognition in aged beagle dogs - A model of sporadic Alzheimer's disease  
    Heliyon 29;9(8):e18443, (2023) 
  • Muschol M, Hoyer W 
    Amyloid oligomers as on-pathway precursors or off-pathway competitors of fibrils 
    Front Mol Biosci 10, 1120416 (2023) 
  • Pils M, Dybala A, Rehn F, Blömeke L, Bujnicki T, Kraemer-Schulien V, Hoyer W, Riesner D, Willbold D, Bannach O 
    Development and implementation of an internal quality control sample to standardize oligomer-based diagnostics of Alzheimer's disease 
    Diagnostics 13, 1702 (2023) 
  • Rezaei-Ghaleh N, Amininasab M, Giller K, Becker S 
    Familial Alzheimer's Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates 
    J Phys Chem Lett 14, 1427-1435 (2023) 
  • Willuweit A, Humpert S, Schöneck M, Endepols H, Burda N, Gremer L, Gering I, Kutzsche J, Shah NJ, Langen KJ, Neumaier B, Willbold D, Drzezga A. 
    Evaluation of the 18F-labeled analog of the therapeutic all-D-enantiomeric peptide RD2 for amyloid β imaging  
    Eur J Pharm Sci 184:106421, (2023) 
  • Kass B, Schemmert S, Zafiu C, Pils M, Bannach O, Kutzsche J, Bujnicki T, Willbold D. 
    Aβ oligomer concentration in mouse and human brain and its drug-induced reduction ex vivo. 
    Cell Rep Med. 3(5):100630, (2022) 
  • Nedaei H, Rezaei-Ghaleh N, Giller K, Becker S, Karami L, Moosavi-Movahedi AA, Griesinger C, Saboury AA 
    The calcium-free form of atorvastatin inhibits amyloid-β(1-42) aggregation in vitro 
    J Biol Chem 298, 101662 (2022) 
  • Bocharov, E. V., L. Gremer, A. S. Urban, I. S. Okhrimenko, P. E. Volynsky, K. D. Nadezhdin, O. V. Bocharova, D. A. Kornilov, Y. A. Zagryadskaya, A. V. Kamynina, P. K. Kuzmichev, J. Kutzsche, N. Bolakhrif, A. Müller-Schiffmann, N. A. Dencher, A. S. Arseniev, R. G. Efremov, V. I. Gordeliy and D. Willbold 
    All-d-Enantiomeric Peptide D3 Designed for Alzheimer’s Disease Treatment Dynamically Interacts with Membrane-Bound Amyloid-β Precursors. 
    Journal of Medicinal Chemistry , (2021) 
  • Camargo LC, Honold D, Bauer R, Shah NJ, Langen KJ, Willbold D, Kutzsche J, Willuweit A, Schemmert S. 
    Sex-Related Motor Deficits in the Tau-P301L Mouse Model 
    Biomedicines 9(9):1160, (2021) 
  • Camargo LC, Schöneck M, Sangarapillai N, Honold D, Shah NJ, Langen KJ, Willbold D, Kutzsche J, Schemmert S, Willuweit A 
    PEAβ Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer's Disease 
    Int J Mol Sci. 22(13):706, (2021) 
  • Gomes CM, Hoyer W, Luo J 
    Editorial: The Biochemistry of Amyloids in Neurodegenerative Diseases, Volume I 
    Front Neurosci 15, 819481 (2021) 
  • König AS, Rösener NS, Gremer L, Tusche M, Flender D, Reinartz E, Hoyer W, Neudecker P, Willbold D, Heise H 
    Structural details of amyloid β oligomers in complex with human prion protein as revealed by solid-state MAS NMR spectroscopy 
    J Biol Chem 296, 100499 (2021) 
  • Mamone S, Glöggler S, Becker S, Rezaei-Ghaleh N 
    Early Divergence in Misfolding Pathways of Amyloid-Beta Peptides 
    ChemPhysChem 22, 2158-2163 (2021) 
  • Schemmert S, Camargo LC, Honold D, Gering I, Kutzsche J, Willuweit A, Willbold D 
    n Vitro and In Vivo Efficacies of the Linear and the Cyclic Version of an All-d-Enantiomeric Peptide Developed for the Treatment of Alzheimer's Disease 
    Int J Mol Sci. 22(12):6553, (2021) 
  • Schützmann MP, Hasecke F, Bachmann S, Zielinski M, Hänsch S, Schröder GF, Zempel H, Hoyer W 
    Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting 
    Nat Commun 12, 4634 (2021) 
  • Vemulapalli SPB, Becker S, Griesinger C, Rezaei-Ghaleh N 
    Combined High-Pressure and Multiquantum NMR and Molecular Simulation Propose a Role for N-Terminal Salt Bridges in Amyloid-Beta 
    J Phys Chem Lett 12, 9933-9939 (2021) 
  • Willbold D, Strodel B, Schröder GF, Hoyer W, Heise H 
    Amyloid-type protein aggregation and prion-like properties of amyloids 
    Chem Rev 121, 8285-8307 (2021) 
  • Elfgen A, Santiago-Schübel B, Hupert M, Schemmert S, Schartmann E, Tusche M, Gering I, Zafiu C, Kutzsche J. 
    Oral absorption enhancement of the amyloid-β oligomer eliminating compound RD2 by conjugation with folic acid  
    Eur J Pharm Sci. , (2020) 
  • Kutzsche J, Jürgens D, Willuweit A, Adermann K, Fuchs C, Simons S, Windisch M, Hümpel M, Rossberg W, Wolzt M, Willbold D. 
    Safety and Pharmacokinetics of the Orally Available Antiprionic Compound PRI-002: A Single and Multiple Ascending Dose Phase I Study 
    Alzheimers Dement (N Y) , 20;6(1):e12001 (2020) 
  • Röder C, Kupreichyk T, Gremer L, Schäfer LU, Pothula KR, Ravelli RBG, Willbold D, Hoyer W, Schröder GF 
    Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils 
    Nat. Struct. Mol. Biol. 27, 660-667 (2020) 
  • Rösener NS, Gremer L, Wördehoff MM, Kupreichyk T, Etzkorn M, Neudecker P, Hoyer W 
    Clustering of human prion protein and α-synuclein oligomers requires the prion protein Nterminus 
    Commun. Biol. 3, 365 (2020) 
  • Dieter Willbold and Janine Kutzsche 
    Do We Need Anti-Prion Compounds to Treat Alzheimer’s Disease? 
    Molecules 24, 2237 (2019) 
  • Elfgen A, Hupert M, Bochinsky K, Tusche M, González de San Román Martin E, Gering I, Sacchi S, Pollegioni L, Huesgen PF, Hartmann R, Santiago-Schübel B, Kutzsche J, Willbold D. 
    Metabolic resistance of the D-peptide RD2 developed for direct elimination of amyloid-β oligomers 
    Sci Rep 9(1), 5715 (2019) 
  • Perez C, Miti T, Hasecke F, Meisl G, Hoyer W, Muschol M, Ullah G 
    Mechanism of fibril and soluble oligomer formation in amyloid β and hen egg white lysozyme proteins 
    J. Phys. Chem. B 123, 5678-5689 (2019) 
  • Schemmert S, Schartmann E, Honold D, Zafiu C, Ziehm T, Langen KJ, Shah NJ, Kutzsche J, Willuweit A, Willbold D. 
    Deceleration of the neurodegenerative phenotype in pyroglutamate-Aβ accumulating transgenic mice by oral treatment with the Aβ oligomer eliminating compound RD2. 
    Neurobiol Dis. 124, 36-45 (2019) 
  • Schemmert S, Schartmann E, Zafiu C, Kass B, Hartwig S, Lehr S, Bannach O, Langen KJ, Shah NJ, Kutzsche J, Willuweit A, Willbold D. 
    Aβ Oligomer Elimination Restores Cognition in Transgenic Alzheimer's Mice with Full-blown Pathology. 
    Mol Neurobiol. 56(3):, 2211-2223 (2019) 
  • Zhang T, Gering I, Kutzsche J, Nagel-Steger L, Willbold D. 
    Toward the Mode of Action of the Clinical Stage All-d-Enantiomeric Peptide RD2 on Aβ42 Aggregation. 
    ACS Chem Neurosci. 10(12), 4800-4809. (2019) 
  • Zhang T, Loschwitz J, Strodel B, Nagel-Steger L, Willbold D. 
    Interference with Amyloid-β Nucleation by Transient Ligand Interaction. 
    Molecules 24(11), pii: E2129 (2019) 
  • Zhang T, Nagel-Steger L, Willbold D. 
    Solution-Based Determination of Dissociation Constants for the Binding of Aβ42 to Antibodies. 
    ChemistryOpen 8(7), 989-994 (2019) 
  • Cavini IA, Munte CE, Erlach MB, van Groen T, Kadish I, Zhang T, Ziehm T, Nagel-Steger L, Kutzsche J, Kremer W, Willbold D, Kalbitzer HR. 
    Inhibition of amyloid Aβ aggregation by high pressures or specific d-enantiomeric peptides. 
    Chem Commun (Camb). 54(26), 3294-3297 (2018) 
  • Dunkelmann T, Teichmann K, Ziehm T, Schemmert S, Frenzel D, Tusche M, Dammers C, Jürgens D, Langen KJ, Demuth HU, Shah NJ, Kutzsche J, Willuweit A, Willbold D 
    Aβ oligomer eliminating compounds interfere successfully with pEAβ (3–42) induced motor neurodegenerative phenotype in transgenic mice 
    Neuropeptides 67, 27-35 (2018) 
  • Dunkelmann T, Schemmert S, Honold D, Teichmann K, Butzküven E, Demuth HU, Shah NJ, Langen KJ, Kutzsche J, Willbold D, Willuweit A. 
    Comprehensive Characterization of the Pyroglutamate Amyloid-β Induced Motor Neurodegenerative Phenotype of TBA2.1 Mice. 
    J Alzheimers Dis. 63(1), 115-130 (2018) 
  • Hasecke F, Miti T, Perez C, Barton J, Schölzel D, Gremer L, Grüning CSR, Matthews G, Meisl G, Knowles TPJ, Willbold D, Neudecker P, Heise H, Ullah G, Hoyer W, Muschol M 
    Origin of metastable oligomers and their effects on amyloid fibril self-assembly 
    Chem. Sci. 9, 5937-5948 (2018) 
  • Kulawik A,Heise H,Zafiu C,Willbold D,Bannach O. 
    Advancements of the sFIDA method for oligomer-based diagnostics of neurodegenerative diseases 
    FEBS Letters , (2018) 
  • Rösener NS, Gremer L, Reinartz E, König A, Brener O, Heise H, Hoyer W, Neudecker P, Willbold D 
    A d-enantiomeric peptide interferes with heteroassociation of amyloid-β oligomers and prion protein 
    J. Biol. Chem. 293, 15748-15764 (2018) 
  • Schartmann E, Schemmert S, Niemietz N, Honold D, Ziehm T, Tusche M, Elfgen A, Gering I, Brener O, Shah NJ, Langen KJ, Kutzsche J, Willbold D, Willuweit A. 
    In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer's Disease. 
    J Alzheimers Dis 64(3), 859-873 (2018) 
  • Zhang T, Pauly T, Nagel-Steger L 
    Stoichiometric Zn2+ interferes with the self-association of Aβ42: Insights from size distribution analysis. 
    Int J Biol Macromol 113, 631-639 (2018) 
  • Dammers C, Reiss K, Gremer L, Lecher J, Ziehm T, Stoldt M, Schwarten M, Willbold D.  
    Pyroglutamate-modified amyloid-β(3-42) shows α-helical intermediates before amyloid formation. 
    Biophys. J. 112, 1621-1633 (2017) 
  • Dammers C, Schwarten M, Buell AK, Willbold D 
    Pyroglutamate-modified Aβ(3-42) affects aggregation kinetics of Aβ(1-42) by accelerating primary and secondary pathways 
    Chem. Sci. 8, 4996-5004 (2017) 
  • Elfgen A, Santiago-Schübel B, Gremer L, Kutzsche J, Willbold, D 
    Surprisingly high stability of the Aβ oligomer eliminating all-D-enantiomeric peptide D3 in media simulating the route of orally administered drugs 
    European Journal of Pharmaceutical Sciences 107, 203-207 (2017) 
  • Gremer L, Schölzel D, Schenk C, Reinartz E, Labahn J, Ravelli RB, Tusche M, Lopez-Iglesias C, Hoyer W, Heise H, Willbold D, Schröder GF 
    Fibril structure of amyloid-ß(1-42) by cryoelectron microscopy 
    Science 358, 116-119 (2017) 
  • Herrmann Y, Kulawik A, Kühbach K, Hülsemann M, Peters L, Bujnicki T, Kravchenko K, Linnartz C, Willbold J, Zafiu C, Bannach O, Willbold D. 
    sFIDA automation yields sub-femtomolar limit of detection for Aβ aggregates in body liquids. 
    Clinical Biochem. 50(4-5), 244-247 (2017) 
  • Klein AN, Ziehm T, van Groen T, Kadish I, Elfgen A, Tusche M, Thomaier M, Reiss K, Brener O, Gremer L, Kutzsche J, Willbold D 
    Optimization of D-peptides for Aβ monomer binding specificity enhances their potential to eliminate toxic Aβ oligomers 
    ACS Chem Neurosci 8, 1889-1900 (2017) 
  • Kravchenko K, Kulawik A, Hülsemann M, Kühbach K, Zafiu C, Herrmann Y, Linnartz C, Peters L, Bujnicki T, Willbold J, Bannach O, Willbold D.  
    Analysis of anticoagulants for blood-based quantitation of amyloid β oligomers in the sFIDA assay. 
    Biol. Chem. 398(4), 465-475 (2017) 
  • Kühbach K, Hülsemann M, Herrmann Y, Kravchenko K, Kulawik A, Linnartz C, Peters L, Wang K, Willbold J, Willbold D, Bannach O.  
    Application of an amyloid beta oligomer standard in the sFIDA assay. 
    In: Biomarkers of Alzheimer's Disease: The Present and the Future. Eds. Sylvain Lehmann, Charlotte Elisabeth Teunissen. , 39-44 (2017) 
    ISBN 9782889450411  
  • Kutzsche J, Schemmert S, Tusche M, Neddens J, Rabl R, Jürgens D, Brener O, Willuweit A, Hutter-Paier B, Willbold D. 
    Large-Scale Oral Treatment Study with the Four Most Promising D3-Derivatives for the Treatment of Alzheimer's Disease. 
    Molecules 22(10), (2017) 
  • Schartmann E, Schemmert S, Ziehm T, Leithold LHE, Jiang N, Tusche M, Shah NJ, Langen KJ, Kutzsche J, Willbold D, Willuweit A. 
    Comparison of blood-brain barrier penetration efficiencies between linear and cyclic all-d-enantiomeric peptides developed for the treatment of Alzheimer's disease. 
    Eur J Pharm Sci. 17, 0928-0987 (2017) 
  • van Groen T, Schemmert S, Brener O, Gremer L, Ziehm T, Tusche M, Nagel-Steger L, Kadish I, Schartmann E, Elfgen A, Jürgens D, Willuweit A, Kutzsche J, Willbold D. 
    The Aβ oligomer eliminating D-enantiomeric peptide RD2 improves cognition without changing plaque pathology. 
    Sci Rep. 7, 16275 (2017) 
  • Wolff M, Zhang-Haagen B, Decker C, Barz B, Schneider M, Biehl R, Radulescu A, Strodel B, Willbold D, Nagel-Steger L 
    Aβ42 pentamers/hexamers are the smallest detectable oligomers in solution 
    Sci Rep 7, 2493 (2017) 
  • Anđela Šarić, Alexander K. Buell, Georg Meisl, Thomas C. T. Michaels, Sara Linse, Tuomas P. J. Knowles and Daan Frenkel 
    Physical determinants for the self-replication of protein fibrils 
    Nature Physics 12, 874-880 (2016) 
  • Barz B and Strodel B 
    Understanding Amyloid-β oligomerization at the molecular level: the role of the fibril surface. 
    Chem. Eur. J. 22, 8768-8772 (2016) 
  • Carballo-Pacheco M and Strodel B 
    Advances in the Simulation of Protein Aggregation at the Atomistic Scale 
    J. Phys. Chem. B 120, 2991–2999 (2016) 
  • Donner L, Fälker K, Gremer L, Klinker S, Pagani G, Ljungberg LU, Lothmann K,Rizzi F, Schaller M, Gohlke H, Willbold D, Grenegard M, Elvers M. 
    Platelets contribute to amyloid-β aggregation in cerebral vessels through integrin αIIbβ3-induced outside-in signaling and clusterin release 
    Sci Signal 9(429), ra52 (2016) 
  • Hülsemann M, Zafiu C, Kühbach K, Lühmann N, Herrmann Y, Peters L, Linnartz C, Willbold J, Kravchenko K, Kulawik A, Willbold S, Bannach O, Willbold D.  
    Biofunctionalized Silica Nanoparticles: Standards in Amyloid-β Oligomer-Based Diagnosis of Alzheimer's Disease. 
    J. Alzheimers Dis. 54, 79-88 (2016) 
  • Klein AN, Ziehm T, Tusche M, Buitenhuis J, Bartnik D, Boeddrich A, Wiglenda T, Wanker E, Funke SA, Brener O, Gremer L, Kutzsche J, Willbold D. 
    Optimization of the All-D Peptide D3 for Aβ Oligomer Elimination. 
    PLoS One 11(4), (2016) 
    Erratum in: PLoS One. 2016;11(7):e0158960. http://dx.doi.org/10.1371/journal.pone.0158960 
  • Kühbach K, Hülsemann M, Herrmann Y, Kravchenko K, Kulawik A, Linnartz C, Peters L, Wang K, Willbold J, Willbold D, Bannach O. 
    Application of an Amyloid Beta Oligomer Standard in the sFIDA Assay 
    Front. Neurosci. 10:8, (2016) 
  • Leithold LH, Jiang N, Post J, Niemietz N, Schartmann E, Ziehm T, Kutzsche J, Shah NJ, Breitkreutz J, Langen KJ, Willuweit A, Willbold D.  
    Pharmacokinetic properties of tandem D-peptides designed for treatment of Alzheimer's disease 
    Eur. J. Pharm. Sci. 89, 31-38 (2016) 
  • Leithold LH, Jiang N, Post J, Ziehm T, Schartmann E, Kutzsche J, Shah NJ, Breitkreutz J, Langen KJ, Willuweit A, Willbold D. 
    Pharmacokinetic Properties of a Novel D-Peptide Developed to be Therapeutically Active Against Toxic β-Amyloid Oligomers 
    Pharm Res. 33, 328-336 (2016) 
  • Mirecka EA, Feuerstein S, Gremer L, Schröder GF, Stoldt M, Willbold D, Hoyer W. 
    β-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor 
    Sci. Rep. 6, 33474 (2016) 
  • Nagel-Steger L, Owen MC, and Strodel B 
    An account of amyloid oligomers: facts and figures obtained from experiments and simulations 
    ChemBioChem 17, 657-676 (2016) 
  • Nouri K, Fansa EK, Amin E, Dvorsky R, Gremer L, Willbold D, Schmitt L, Timson DJ, Ahmadian MR. 
    IQGAP1 interaction with RHO family proteins revisited: Kinetic and equilibrium evidence for multiple distinct binding sites 
    J Biol Chem , (2016) 
    [Epub ahead of print] 
  • Orr AA, Wördehoff MM, Hoyer W, Tamamis P 
    Uncovering the binding and specificity of β-wrapins for amyloid-β and α-synuclein 
    J. Phys. Chem. B 120, 12781-12794 (2016) 
  • Owen MC, Strodel B, Csizmadia IG & Viskolcz B 
    Radical Formation Initiates Solvent-Dependent Unfolding and β-Sheet Formation in a Model Helical Peptide 
    J. Phys. Chem. B 120, 4878-4889 (2016) 
  • Rudolph S, Klein AN, Tusche M, Schlosser C, Elfgen A, Brener O, Teunissen C,Gremer L, Funke SA, Kutzsche J, Willbold D. 
    Correction: Competitive Mirror Image Phage Display Derived Peptide Modulates Amyloid Beta Aggregation and Toxicity 
    PLoS One 11(7), (2016) 
  • Streich C, Akkari L, Decker C, Bormann J, Rehbock C, Müller-Schiffmann A, Niemeyer FC, Nagel-Steger L, Willbold D, Sacca B, Korth C, Schrader T, Barcikowski S.  
    Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation. 
    ACS Nano 10, 7582-7597 (2016) 
  • Thomaier M, Gremer L, Dammers C, Fabig J, Neudecker P, Willbold D. 
    High-Affinity Binding of Monomeric but Not Oligomeric Amyloid-β to Ganglioside GM1 Containing Nanodiscs 
    Biochemistry , (2016) 
  • Wallin C, Kulkarni YS, Abelein A, Jarvet J, Liao Q, Strodel B, Olsson L, Luo J, Abrahams JP, Sholts SB, Roos PM, Kamerlin SCL, Gräslund A, Wärmländer SKTS 
    Characterization of Mn(II) ion Binding to the Amyloid-β Peptide in Alzheimer’s Disease 
    J Trace Elem Med Biol , (2016) 
  • Zhang-Haagen B, Biehl R, Nagel-Steger L, Radulescu A, Richter D, Willbold D. 
    Monomeric Amyloid Beta Peptide in Hexafluoroisopropanol Detected by Small Angle Neutron Scattering. 
    PLoS One 11(2), e0150267 (2016) 
  • Ziehm T, Brener O, van Groen T, Kadish I, Frenzel D, Tusche M, Kutzsche J, Reiß K, Gremer L, Nagel-Steger L, Willbold D. 
    Increase of Positive Net Charge and Conformational Rigidity Enhances the Efficacy of d-Enantiomeric Peptides Designed to Eliminate Cytotoxic Aβ Species. 
    ACS Chem Neurosci. 7 (8), 1088–1096 (2016) 
  • Brener O, Dunkelmann T, Gremer L, van Groen T, Mirecka EA, Kadish I, Willuweit A, Kutzsche J, Jürgens D, Rudolph S, Tusche M, Bongen P, Pietruszka J, Oesterhelt F, Langen K-J, Demuth H-U, Janssen A, Hoyer W, Funke SA, Nagel-Steger L, Willbold D 
    QIAD assay for quantitating a compound's efficacy in elimination of toxic Aβ oligomers. 
    Sci Rep 5, 13222 (2015) 
  • Dammers C, Gremer L, Neudecker P, Demuth HU, Schwarten M, Willbold D 
    Purification and Characterization of Recombinant N-Terminally Pyroglutamate-Modified Amyloid-β Variants and Structural Analysis by Solution NMR Spectroscopy 
    PLoS One 10, e0139710 (2015) 
  • Dammers C, Gremer L, Reiß K, Klein AN, Neudecker P, Hartmann R, Sun N, Demuth HU, Schwarten M, Willbold D 
    Structural Analysis and Aggregation Propensity of Pyroglutamate Aβ(3-40) in Aqueous Trifluoroethanol  
    PLoS One 10, e0143647 (2015) 
  • Jiang N, Leithold LH, Post J, Ziehm T, Mauler J, Gremer L, Cremer M, Schartmann E, Shah NJ, Kutzsche J, Langen KJ, Breitkreutz J, Willbold D, Willuweit A 
    Preclinical Pharmacokinetic Studies of the Tritium Labelled D-Enantiomeric Peptide D3 Developed for the Treatment of Alzheimer´s Disease 
    PLoS One 10, e0128553 (2015) 
  • Mandler M, Santic R, Gruber P, Cinar Y, Pichler D, Funke SA, Willbold D, Schneeberger A, Schmidt W, Mattner F 
    Tailoring the antibody response to aggregated Aß using novel Alzheimer-vaccines. 
    PLoS ONE 10, e0115237 (2015) 
  • Pattky M, Nicolardi S, Santiago-Schübel B, Sydes D, van der Burgt YE, Klein AN, Jiang N, Mohrlüder J, Hänel K, Kutzsche J, Funke SA, Willbold D, Willbold S, Huhn C 
    Structure characterization of unexpected covalent O-sulfonation and ion-pairing on an extremely hydrophilic peptide with CE-MS and FT-ICR-MS. 
    Anal. Bioanal. Chem. 407, 6637-6655 (2015) 
  • Shaykhalishahi H, Gauhar A, Wördehoff MM, Grüning CS, Klein A, Bannach O, Stoldt M, Willbold D, Härd T, Hoyer W 
    Contact between the beta1 and beta2 segments of alpha-synuclein that inhibits amyloid formation 
    Angew. Chem. Int. Ed. 54, 8837-8840 (2015) 
  • Shaykhalishahi H, Mirecka EA, Gauhar A, Grüning CSR, Willbold D, Härd T, Stoldt M, Hoyer W 
    A beta-hairpin-binding protein for three different disease-related amyloidogenic proteins 
    ChemBioChem 16, 411-414 (2015) 
  • Wolff M, Unuchek D, Zhang B, Gordeliy V, Willbold D, Nagel-Steger L 
    Amyloid β oligomeric species present in the lag phase of amyloid formation. 
    PLoS ONE 10, e0127865 (2015) 
  • Frenzel D, Glück JM, Brener O, Oesterhelt F, Nagel-Steger L, Willbold D 
    Immobilization of homogeneous monomeric, oligomeric and fibrillar Aβ species for reliable SPR measurements 
    PLoS ONE 9, e89490 (2014) 
  • Frenzel D, Willbold D 
    Kinetic titration series with biolayer interferometry 
    PLoS ONE 9, e106882 (2014) 
  • Grüning CS, Mirecka EA, Klein AN, Mandelkow E, Willbold D, Marino SF, Stoldt M, Hoyer W 
    Alternative conformations of the tau repeat domain in complex with an engineered binding protein 
    J. Biol. Chem. 289, 23209-23218 (2014) 
  • Mirecka EA, Shaykhalishahi H, Gauhar A, Akgül S, Lecher J, Willbold D, Stoldt M, Hoyer W 
    Sequestration of a beta-hairpin for control of alpha-synuclein aggregation 
    Angew. Chem. Int. Ed. 53, 4227-4230 (2014) 
  • Olubiyi OO, Frenzel D, Bartnik D, Glück JM, Brener O, Nagel-Steger L, Funke SA, Willbold D, Strodel B 
    Amyloid aggregation inhibitory mechanism of arginine-rich D-peptides 
    Curr. Med. Chem. 21, 1448-1457 (2014) 
  • Widera M, Klein NA, Cinar Y, Funke SA, Willbold D, Schaal H 
    The D-amino acid peptide D3 reduces amyloid fibril boosted HIV-1 infectivity 
    AIDS Res. Therapy 11, 1 (2014) 
  • Dornieden S, Müller-Schiffmann A, Sticht H, Cinar Y, Wördehoff M, Korth C, Funke SA, Willbold D 
    Characterization of a single-chain variable fragment recognizing a linear epitope of Aß: A biotechnical tool for studies on Alzheimer's disease? 
    PLoS ONE 8, e59820 (2013) 
  • Grüning CS, Klinker S, Wolff M, Schneider M, Toksöz K, Klein AN, Nagel-Steger L, Willbold D, Hoyer W 
    The off-rate of monomers dissociating from amyloid-beta protofibrils 
    J. Biol. Chem. 288, 37104-37111 (2013) 
  • van Groen T, Kadish I, Funke SA, Bartnik D, Willbold D 
    Treatment with D3 removes amyloid deposits, reduces inflammation, and improves cognition in old AβPP/PS1 double transgenic mice. 
    J Alzheimer's Dis. 34, 609-620 (2013) 
    open access  
  • Wang-Dietrich L, Funke SA, Kühbach K, Wang K, Besmehn A, Willbold S, Cinar Y, Bannach O, Birkmann E, Willbold D 
    The Aβ oligomer count in CSF is a biomarker for Alzheimer’s disease. 
    J. Alzheimers Dis. 34, 985-994 (2013) 
  • Funke SA, Bartnik D, Glück JM, Pirkowska K, Wiesehan K, Weber U, Gulyas B, Halldin C, Pfeifer A, Spenger C, Muhs A, Willbold D 
    Development of a small D-enantiomeric Alzheimer's amyloid-beta binding peptide ligand for future in vivo imaging applications. 
    PLoS ONE 7, e41457 (2012) 
  • Funke SA, Liu H, Sehl T, Bartnik D, Brener O, Nagel-Steger L, Wiesehan K, Willbold D 
    Identification and characterization of an Aβ oligomer precipitating peptide that may be useful to explore gene therapeutic approaches to Alzheimer’s disease. 
    Rejuv. Res. 15, 144-147 (2012) 
  • Funke SA, Willbold D 
    Peptides for Therapy and Diagnosis of Alzheimer’s Disease. 
    Curr. Pharm. Design 18, 755-767 (2012) 
  • Jahan M, Nag S, Krasikova R, Weber U, Muhs A, Pfeifer A, Spenger C, Willbold D, Gulyás B, Halldin C 
    Fluorine-18 labeling of three novel d-peptides by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate and preliminary examination by postmortem whole-hemisphere human brain autoradiography. 
    Nucl. Med. Biol. 392, 315-323 (2012) 
  • Kroth H, Ansaloni A, Varisco Y, Jan A, Sreenivasachary N, Rezaei-Ghaleh N, Giriens V, Lohmann S, Pilar López-Deber M, Adolfsson O, Pihlgren M, Paganetti P, Froestl W, Nagel-Steger L, Willbold D, Schrader T, Zweckstetter M, Pfeifer A, Lashuel HA, Muhs A 
    Discovery and structure activity relationship of small molecule inhibitors of toxic β-amyloid-42 fibril formation. 
    J. Biol. Chem. 287, 34786-34800 (2012) 
  • Mazargui H, Lévêque C, Bartnik D, Fantini J, Gouget T, Melone MA, Funke SA, Willbold D, Perrone L 
    A synthetic amino acid substitution of Tyr10 in Aβ peptide sequence yields a dominant negative variant in amyloidogenesis. 
    Aging Cell 11, 530-541 (2012) 
  • Neudecker P, Robustelli P, Cavallli A, Walsh P, Lundstrom P, Zarrine-Afsar A, Sharpe S, Vendruscolo M, Kay LE 
    Structure of an intermediate state in protein folding and aggregation. 
    Science 336, 362-366 (2012) 
  • Sun N, Funke SA, Willbold D 
    A survey of peptides with effective therapeutic potential in Alzheimer’s disease rodent models or in human clinical studies. 
    Mini. Rev. Med. Chem. 12, 388-398 (2012) 
    full text open access  
  • Sun N, Funke SA, Willbold D 
    Mirror image phage display - Generating stable therapeutically and diagnostically active peptides with biotechnological means. 
    J. Biotech. 161, 121-125 (2012) 
    full text  
  • Sun N, Hartmann R, Lecher J, Stoldt M, Funke SA, Gremer L, Ludwig H-H, Demuth H-U, Kleinschmidt M, Willbold D 
    Structural analysis of the pyroglutamate modified isoform of the Alzheimer's disease related beta-amyloid using NMR spectroscopy. 
    J. Pept. Science 18, 691-695 (2012) 
  • van Groen T, Kadish I, Funke A, Bartnik D, Willbold D 
    Treatment with Aβ42 Binding d-Amino Acid Peptides Reduce Amyloid Deposition and Inflammation in APP/PS1 Double Transgenic Mice. 
    Adv. Protein. Chem. Struct. Biol. 88, 133-152 (2012) 
  • Funke SA 
    Detection of Soluble Amyloid-β Oligomers and Insoluble High-Molecular-Weight Particles in CSF: Development of Methods with Potential for Diagnosis and Therapy Monitoring of Alzheimer's Disease. 
    Int J Alzheimers Dis. 2011, 151645 (2011) 
  • Funke SA, Willbold D 
    Quantitation of Amyloid-β oligomers in human body fluids for Alzheimer’s disease early diagnosis or therapy monitoring. 
    Alzheimer's diagnosis. Charles E. Ronson (Ed.), Hauppage, NY, USA (2011) 
    Nova Science Publishers, ISBN 978-1-61209-846-3 
  • Hickman DT, López-Deber MP, Ndao DM, Silva AB, Nand D, Pihlgren M, Giriens V, Madani R, St-Pierre A, Karastan H, Nagel-Steger L, Willbold D, Riesner D, Nicolau C, Baldus M, Pfeifer A, Muhs A 
    Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases. 
    J. Biol.Chem. 286, 13966-13976 (2011) 
  • Hochdörffer K, März-Berberich J, Nagel-Steger L, Epple M, Meyer-Zaika W, Horn AH, Sticht H, Sinha S, Bitan G, Schrader T 
    Rational Design of β-Sheet Ligands Against Aβ(42)-Induced Toxicity. 
    J. Am. Chem. Soc. 133, 4348-4358 (2011) 
  • van Groen T, Kadish I, Funke A and Willbold D 
    Staining of Amyloid Beta (Abeta) Using (Immuno) Histochemical Techniques and Abeta42 Specific Peptides 
    In: Neuroimaging for Clinicians - Combining Research and Practice. In Tech. Editor: Julio F. P. Peres; ISBN 978-953-307-450-4, Chapter 4 (2011) 
    free download  
  • Bartnik D, Funke SA, Andrei-Selmer L-C, Bacher M, Dodel R, Willbold D 
    Differently selected D-enantiomeric peptides act on different Aß species. 
    Rejuvenation Res. 13, 202-205 (2010) 
  • Funke SA, van Groen T, Kadish I, Bartnik D, Nagel-Steger L, Brener O, Sehl T, Batra-Safferling R, Moriscot C, Schoehn G, Horn AHC, Müller-Schiffmann A, Korth C, Sticht H, Willbold D 
    Oral Treatment with the D-Enantiomeric Peptide D3 Improves Pathology and Behavior of Alzheimer’s disease Transgenic Mice 
    ACS Chem. Neurosci. 1, 639-648 (2010) 
    Highlighted in: Chemical & Engineering News, 88(33), August 16, 2010 
  • Funke SA, Wang L, Birkmann E, Willbold D 
    Single particle detection system for Aß: Adaptation of surface-FIDA to laser scanning microscopy. 
    Rejuvenation Res. 13, 206-209 (2010) 
  • Liu HM, Funke SA, Willbold D 
    Transport of Alzheimer's disease amyloid-ß peptide binding D-amino acid peptides across a blood-brain barrier in vitro model. 
    Rejuvenation Res. 13, 210-213 (2010) 
  • Luheshi LM, Hoyer W, de Barros TP, van Dijk-Härd I, Brorsson AC, Macao B, Persson C, Crowther DC, Lomas DA, Ståhl S, Dobson CM, Härd T 
    Sequestration of the Abeta peptide prevents toxicity and promotes degradation in vivo 
    PLoS Biol. 8, e1000334 (2010) 
  • Müller-Schiffmann A, März-Berberich J, Andrjevna A, Rönicke R, Bartnik D, Brener O, Kutzsche J, Horn AHC, Hellmert M, Polkowska J, Gottmann K, Reymann K, Funke SA, Nagel-Steger L, Moriscot C, Schoehn G, Sticht H, Willbold D, Schrader T, Korth C 
    Combining independent drug classes into superior, synergistically acting hybrid molecules. 
    Angew. Chem. Int. Ed. Engl. 49, 8743-8746 (2010) 
  • Nagel-Steger L, Demeler B, Meyer-Zaika W, Hochdörffer K, Schrader T, Willbold D 
    Modulation of aggregate size- and shape-distributions of the amyloid-beta peptide by a designed ß-sheet breaker. 
    Eur. Biophys. J. 39, 415-422 (2010) 
  • Demeler B, Brookes E, Nagel-Steger L  
    Analysis of heterogeneity in molecular weight and shape by analytical ultracentrifugation using parallel distributed computing. 
    Meth. Enzymol. 454, 87-113 (2009) 
  • Funke SA, Birkmann E, Willbold D 
    Detection of Amyloid-β aggregates in body fluids: A suitable method for early diagnosis of Alzheimer's diesease? 
    Curr. Alzheimer Res. 6, 285-289 (2009) 
  • Funke SA, Willbold D 
    Mirror image phage display - a method to generate D-peptide ligands for use in diagnostic or therapeutical applications? 
    Mol. BioSyst. 5, 783-786 (2009) 
  • Görtz P, Opatz J, Siebler M, Funke SA, Willbold D, Lange-Asschenfeldt C 
    Transient reduction of spontaneous neuronal network activity by sublethal amyloid beta (1-42) peptide concentrations. 
    J. Neural Transmission 116, 351-355 (2009) 
  • Schlenzig D, Manhart S, Cinar Y, Willbold D, Funke SA, Kleinschmidt M, Hause G, Schilling S, Demuth H-U 
    Pyroglutamate formation influences solubility and amyloidenicity of amyloid peptides. A driving force in different neurodegenerative disorders? 
    Biochemistry 48, 7072-7078 (2009) 
  • van Groen T, Kadish I, Wiesehan K, Funke, SA, Willbold D 
    In vitro and in vivo staining characteristics of small, fluorescent, Aß42 binding D-enantiomeric peptides in transgenic AD mouse models. 
    ChemMedChem 4, 276-282 (2009) 
  • Birkmann E, Henke F, Funke SA, Bannach O, Riesner D, Willbold D 
    A highly sensitive diagnsotic assay for aggregate-related diseases e.g. prion disease and Alzheimer's disease. 
    Rejuvenation Res. 11, 359-363 (2008) 
  • Funke SA, Birkmann E, Henke F, Görtz P, Lange-Asschenfeldt C, Riesner D, Willbold D 
    An ultra sensitive assay for early diagnosis of Alzheimer's disease. 
    Rejuvenation Res. 11, 315-318 (2008) 
  • Nagel-Steger L, Demeler B, Hochdörfer K, Schrader T, Willbold D 
    Modulation of aggregate size and shape distributions of amyloid-ß peptide solutions by a designed ß-sheet breaker. 
    NIC Workshop 2008 (From Computational Biophysics to Systems Biology; CBSB08) Vol. 40, (2008) 
  • van Groen T, Wiesehan K, Funke SA, Kadish I, Nagel-Steger L, Willbold D 
    Reduction of Alzheimer's disease amyloid plaque load in transgenic mice by D3, a D-enantiomeric peptide identified by mirror image phage display. 
    ChemMedChem 3, 1848-1852 (2008) 
    [This article was evaluated by the faculty of 1000 Biology as a "must read"]  
  • Wiesehan K, Stöhr J, Nagel-Steger K, van Groen T, Riesner D and Willbold D 
    Inhibition of cytotoxicity and fibril formation by a D-amino acid peptide that specifically binds to Alzheimer's disease amyloid peptide 
    Prot. Eng. Des. Sel. 21, 241-246 (2008) 
  • Funke SA, Birkmann E, Henke F, Görtz P, Lange-Asschenfeldt C, Riesner D, Willbold D, 
    Single particle detection of amyloid-ß aggregates associated with Alzheimer's disease. 
    Biochem. Biophys. Res. Comm. 364, 902-907 (2007) 
  • Muhs A, Hickmann DT, Pihlgren M, Chuard N, Giriens V, Meerschman C, van der Auwera I, van Leuven F, Sugawara M, Weingertner MC, Bechinger B, Greferath R, Kolonko N, Nagel-Steger L, Riesner D, Brady RO, Pfeifer A, Nicolau C 
    Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice 
    Proc. Natl. Acad. Sci. 104, 9810-9815 (2007) 
  • Nagel-Steger L, Demeler B, Willbold D 
    Aggregate size and shape distributions in amyloid-ß peptide solutions. Aggregate Size and Shape Distributions in Amyloid-beta Peptide Solutions. 
    NIC Workshop (From Computational Biophysics to Systems Biology; CBSB07) Vol. 36, (2007) 
  • Wiesehan K, Funke SA, Fries M, Willbold D 
    Purification of recombinantly expressed and cytotoxic human amyloid-beta peptide. 
    J. Chrom. B 856, 229-233 (2007) 
  • Wiesehan K, Buder K, Linke RP, Patt S, Stoldt M, Unger E, Schmitt B, Bucci E and Willbold D 
    Selection of D-amino-acid peptides that bind to Alzheimer's disease amyloid peptide Abeta(1-42) by mirror image phage display. 
    ChemBioChem 4, 748-753 (2003) 
  • Wiesehan K, Willbold D 
    Mirror image phage display: Aiming at the mirror. 
    ChemBioChem 4, 811-815 (2003) 
  • Willbold D & Wiesehan K 
    Peptid zur Diagnose und Therapie der Alzheimer-Demenz National: DE 10117281A1, international: PCT/EP02/03862 
    , (2001) 
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