Research Grants
The Foundation supports research projects, scientific publications, events, and other activities focussing on the age-related neurodegenerative diseases. Our efforts are directed to translational approaches based on expertise in biology, biochemistry and biophysics to provide mechanistic, pharmacological and methodological insights for future clinical translation of novel, more specific and effective strategies for diagnosis, prevention and therapy. Because of the presently rather low profits from the Foundation's assets the scientific members of the Board recommend research projects that deserve to be funded. It is currently not possible to submit grant applications.
Funded since 2016
Dr. Dr. Florian Raabe, Max-Planck-Institut für Psychiatrie, München
Identification of a miRNA signature from neuron-derived extracellular vesicles to predict disease severity in schizophrenia
New: This project aims to identify a pilot translational microRNA signature, derived from human-induced pluripotent stem cells (iPSCs)-derived neurons and neuron-derived extracellular vesicles obtained from peripheral blood samples, to predict diseases severity in schizophrenia. The neuroscience-based neuronal miRNA signature will help to identify individuals with schizophrenia who exhibit prognostically worse symptoms, particularly cognitive impairments. By establishing a framework for neuroscience-based patient stratification, this project will facilitate the identification of clinically relevant sub-biotypes within schizophrenia, ultimately improving diagnostic strategies to pave the way for more personalized treatment options. The research is funded with 79,600 Euro for two years.
Prof. Dr. Günter Höglinger, Neurologische Klinik und Poliklinik, LMU Klinikum München
Prospective validation of the biological SynNeurGe diagnostic classification criteria for Parkinson’s disease
Running: There is growing hope that disease-modifying treatments could target the molecular basis of Parkinson’s disease (PD) even before the onset of symptoms. Therefore, the team proposes a biologically based classification using a three-component system with the following aspects: Presence of pathological alpha-synuclein, evidence of underlying degeneration, and documentation of pathogenic gene variants. The project addresses the need for a comprehensive validation of these criteria in order to finally transfer the research concept into prospectively validated evidence, enabling the objective diagnosis, classification and staging of PD. The research is funded with 85,000 Euro for two years.
Prof. Dr. Michael Sendtner & PD Dr. Michael Briese, Institut für Klinische Neurobiologie, Würzburg
Antisense oligonucleotide-mediated depletion of axonal tau as a therapeutic strategy for treatment of Alzheimer’s disease
Running: While research so far mostly focused on removing senile plaques, it is becoming clear the neurofibrillary tangles (NFTs) might be more closely associated with the pathological mechanisms underlying Alzheimer’s disease (AD). Thus, halting or preventing NFT formation might be a promising therapeutic option. Several approaches have been developed to regulate the involved tau protein in order to prevent the seeding of NFTs. A suitable option might be to selectively block tau production in order to prevent tau aggregation. To further investigate the validity of this strategy, the group will use an AD mouse model and cultured human cortical neurons for testing. The research project will be funded with 50,000 Euro for 18 months.
PD Dr. Till Adhikary, Institut für Molekularbiologie, Universität Marburg
PD Dr. Axel Weber, Institut für Humangenetik, Universität Gießen
Haplotype-specific chromatin interactions and gene regulation at the genomic MAPT locus (chr17q21.31)
Running: The aggregation of the microtubule-associated protein tau (MAPT) in cells of the central nervous system is associated with different kinds of dementia. As the haplotype chr17q21.31 is hereditary, one assumes that it is a key for the development of the so-called tauopathies. The research should provide first basic data on which further studies can be built upon. The research is funded with 39,000 Euro for one year.
Prof. Dr. Dorothee Dormann, Institut für Molekulare Physiologie, Universität Mainz
Analysis of physiological vs. pathological TDP-43 phosphorylation
Running: TDP-43 is a major pathological protein in several neurodegenerative disorders, most notably ALS and Frontotemporal Dementia. Dysfunction of TDP-43 is thought to drive neurodegeneration. The team recently identified C-terminal TDP-43 phosphorylation as potent suppressor of aggregation, raising the question when and how this disease-linked modification is introduced in cells and how it is regulated in health and disease. Too, the team will address the hypothesis that TDP-43 might be preferentially phosphorylated in the phase separated or aggregated state. This research has the potential to uncover so far elusive “physiological” TDP-43 phosphorylation. The research is funded with 110,000 Euro for two years.
Prof. Dr. Anja Schneider, Deutsches Zentrum für neurodegenerative Erkrankungen, Bonn
Protein misfolding cyclic amplification (PMCA) analysis of plasma and CSF exosomal alpha-synuclein for the diagnosis of Parkinson’s disease and Lewy Body dementia
Running: The team studies exosomes (extracellular vesicles) in neurodegenerative diseases. Of particular interest is the release of toxic, aggregated proteins such as alpha-synuclein and their contribution to toxicity and the spread of disease pathology in the brain. The aim is to use an assay (PMCA) to quantify the potential of exosomal alpha-synuclein from cerebrospinal fluid (CSF) and plasma, to induce the aggregation of alpha-synuclein and to investigate whether this assay can be used as a diagnostic biomarker in Parkinson's disease. This could also enable diagnosis and prognosis in the prodromal and preclinical stage. The research project is funded with 79,800 Euro for two years.
Papers: Chatterjee M et al. (2023) C1q is increased in cerebrospinal fluid-derived extracellular vesicles in Alzheimer’s disease: A multi-cohort proteomics and immuno-assay validation study. Alzheimers Dement 19(11): 4828-40. doi: 10.1002/alz.13066 - Chatterjee M et al. (2024) Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS. Nat Med 30(6): 1771-83. doi: 10.1038/s41591-024-02937
PD Dr. Chi Wang Ip, Neurology, Universitätsklinikum Würzburg
Translational multiomics for a pathophysiological investigation of dystonia: The role of gene-environment interaction in DYT1, DYT6 and DYT25
Finished: Dystonia refers to a group of movement disorders. These disorders can occur due to various causes, including neurodegenerative diseases such as Parkinson’s or Huntington’s. The team used multiomics analyses to systematically investigate the relationship between gene and environmental factors. The results of two mouse models indicate the disruption of central cellular processes in dystonia-relevant brain regions, triggered by peripheral nerve injury. Within the framework of the project, which was also funded by the DFG, one medical and three natural science doctoral theses were successfully completed. The Foundation provided € 60,000 in funding.
Publications: Knorr S et al. (2021) Multifactorial Assessment of Motor Behavior in Rats after Unilateral Sciatic Nerve Crush Injury. J Vis Exp 173. doi: 10.3791/62606 - Rauschenberger L et al. (2021) Second hit hypothesis in dystonia: Dysfunctional cross talk between neuroplasticity and environment. Neurobiol Dis 159. doi: 10.1016/j.nbd.2021. 105511 - Knorr S et al. (2022) Experimental deep brain stimulation in rodent models of movement disorders. Exp Neurol 348. doi: 10.1016/j.exneurol.2021.113926 - Karikari A et al. (2022) Neurodegeneration by alpha-synuclein-specific T cells in AAV-A53T-alpha-synuclein Parkinson’s disease mice. Brain Behav Immun 101. doi: 10.1016/j.bbi. 2022.01.007 - Grotemeyer A et al. (2022) Neuroinflammation in Parkinson’s Disease Putative Pathomechanisms and Targets for Disease-Modification. Front Immunol 13. doi: 10.3389/fimmu.2022.878771 - Rauschenberger L et al. (2022) Age-dependent neurodegeneration and neuroinflammation in a genetic A30P/A53T double-mutated alpha-synuclein mouse model of Parkinson’s disease. Neurobiol Dis 171. doi: 10.1016/j.nbd. 2022.105798 - Rauschenberger L et al. (2023) Peripheral nerve injury elicits microstructural and neurochemical changes in the striatum and substantia nigra of DYT-TOR1A mouse model with dystonia-like movements. Neurobiol Dis 179. doi: 10.1016/j.nbd.2023.106056 - Reinhold C et al. (2024) Gene-environment interaction elicits dystonia-like features and impaired translational regulation in a DYT-TOR1A mouse model. Neurobiol Dis 193. doi: 10.1016/j.nbd.2024.106453 - Knorr S et al. (2024) Disturbed brain energy metabolism in a rodent model of DYT-TOR1A dystonia. Neurobiol Dis 194. doi: 10.1016/j.nbd.2024.106462 - Peach R et al. (2024) Head movement dynamics in dystonia: a multi-centre retrospective study using visuial perceptive deep learning. NPJ Digit Med 7(1):160. doi: 10.1038/s41746-024-01140-6 - Reinhold C et al. (2025) Peripheral nerve injury induces dystonia-like movements and dysregulation in the energy metabolism: A multi-omics descriptive study in Thap1+/- mice. Neurobiol. Dis 205. doi: 10.1016/j.nbd.2024.106783
Dr. Susanne Wegmann, Deutsches Zentrum für Neurodegenerative Erkrankungen, Charité Berlin
Changes in chromatin architecture induced by Tau protein pathology in Alzheimer’s disease
Finished: In Alzheimer’s disease (AD) and tauopathies, the Tau protein accumulates and aggregates in the somatodendritic compartment. Associated with this mislocalization, different disease related changes have been observed in affected neurons. Too, Tau accumulation can impair the transport of proteins and RNA in and out of the nucleus. This was motivation enough to investigate the effect of pathological Tau missorting and aggregation on the 3D-architecture of neuronal chromatin. The team successfully explored alterations in nuclear shape and chromatin architecture and the re-arrangement of chromosomal territories in Tau transgenic mice and in human postmortem AD brain. The findings show that already an increase in Tau levels seems to be sufficient to trigger pro-inflammatory signalling and induce cell death. The project was funded with 78,500 Euro for two years.
Prof. Dr. Robert Perneczky, Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München
Amyloid-beta clearance mechanisms: A multi-modal study on lymphatic, glymphatic and blood-brain-barrier function in Alzheimer’s disease
Finished: The project served to research the complex transport systems of the amyloid beta protein. After initial delays due to the COVID-19 pandemic, the study has now been successfully completed, carrying out valuable additional examinations and including additional study participants with non-Alzheimer neurodegeneration. A total of 82 study participants completed the AD protocol. The largest possible number of these test subjects should be examined after 24 months. The research project was funded with 80,000 Euro.
Publications: Finze A et al. (2023) Individual regional associations between Aβ-, tau- and neurodegeneration (ATN) with microglial activation in patients with primary and secondary tauopathies. Mol Psychiatry. doi: 10.1038/s41380-023-02188-8 § Blennow K et al. (2023) The potential clinical value of plasma biomarkers in Alzheimer’s disease. Alzheimers Dement 19(12):5805-16. doi: 10.1002/alz13455 § Perneczky R et al. (2024) Anti-amyloid antibody treatments for Alzheimer’s disease. Eur J Neurol 31(2):e16049. doi: 10.1111/ene16049 § Perna L et al. (2023) Subjective cognitive complaints and blood biomarkers of neurodegenerative diseases: a longitudinal cohort study. Alzheimers Res Ther 15(1):198. doi: 10.1186/s13195-023-01341-03 § Stockbauer A et al. (2023) Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission. Eur J Nucl Med Mol Imaging. doi: 10.1007/s00259-023-06493-w § Sadlon A et al. (2024) Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults. J Prev Alzheimers Dis 11(1):230-40. doi: 10.14283/jpad.2023.99 § Biechele G et al. (2024) Associations between sex, body mass index and the individual microglial response in Alzheimer’s disease. J Neuroinflammation 21(1):30. doi: 10.1186/s12974-024-03020-y
Prof. Dr. Susanne A. Schneider, Neurology, Ludwig-Maximilians-Universität München
Heterozygous mutations of Niemann-Pick type C predispose to late-onset neurodegeneration – a clinical, radiological and molecular characterization
Finished: The project was dedicated to the study of mutations in a rare genetic condition called Niemann Pick type C (NPC). Because NPC-family history studies suggest a high proportion of late-onset neurodegenerative diseases. Aim was therefore to systematically assess NPC mutation carriers for signs of neurodegeneration. Findings confirm the hypothesis: The studies carried out support the connection between certain genes and and the development of neurodegenerative disease, and the results are highly relevant. The research project was funded with 93,300 Euro for two years.
Publications: Schneider SA et al. (2019) Do heterozygous mutations of Niemann-Pick type C predispose to late-onset neurodegeneration: a review of the literature. J Neurol 268(6):2055-2064. doi: 10.1007/s00415-019-09621-5 ▪ Havla J et al. (2020) Retinal axonal degeneration in Niemann-Pick type C diseases. J Neurol 267(7):2070-2082. doi: 10.1007/s00415-020-09796-2 ▪ Bremova-Ertl T et al. (2020) Clinical, ocular motor, and imaging profile of Niemann-Pick type C heterozygosity. Neurology 94(16):e1702-e1715. doi: 10.1212/WNL.0000000000009290 ▪ Schneider SA & Alcalay RN (2020) Precision medicine in Parkinson’s disease: emerging treatments for genetic Parkinson’s disease. J Neurol 267(3):860-869, doi: 10.1007/s00415-020-09705-7 ▪ Schneider SA et al. (2020) Emerging targeted therapeutics for genetic subtypes of Parkinsonism. Neurotherapeutics 17(4):1378-1392. doi: 10.1007/s13311-020-00920-8 ▪ Colombo A et al. (2021) Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia. Nat Commun 12(1):1158. doi: 10.1038/s41467-021-21428-5 ▪ Bremova-Ertl T et al. (2021) Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C. J Neurol 1-12. doi: 10.1007/s00415-021-10717-0 ▪ Majovska J et al. (2021) Pontocerebellar atrophy is the hallmark neuroradiological finding in late-onset Tay-Sachs disease (submitted)
Prof. Dr. Alexandra Dürr, Institut du Cerveau et de la Moelle Epinière, Paris
Identification of genetic, epigenetic and environmental modifiers in hereditary spastic paraplegia
Finished: Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder with genetic modulators. Aim was to contribute to the further identification of genetic, epigenetic and/or environmental influences that can predict onset, progression and outcome and, thus, lead to the development of new treatments. Comparison of missense and truncating gene mutations revealed a significantly lower age at onset for patients carrying missense mutations. Too, the cohort of patients allowed to identify a significantly younger age at onset in missense mutations carriers and lower penetrance in females, despite more severe disorder. The findings might lead to novel approaches for treatment. The extensive study has been funded with 309,000 Euro for six years.
Publications: Elsayed LE et al. (2016) Hereditary spastic paraplegias: Identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan. Eur J Hum Genet 25(1):100-10. doi: 10.1038/ejhg.2016.108 ▪ Parodi L et al. (2017) Hereditary spastic paraplegia: More than an upper motor neuron diesease. Rev Neurol 173(5):352-60. doi: 10.1016/j.neurol.2017.03.034 ▪ Parodi L et al. (2018) Spastic paraplegia due to SPAST mutations is modified by the underlying mutation and sex. Brain 141(12):3331-42. doi: 10.1093/brain/awy285 ▪ Coarelli G. et al. (2019) Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7. Neurology 92(23):e2670-90. doi: 10.1212/WNL.0000000000007606 ▪ Huin V et al. (2020) Homo-zygous GRN mutations: unexpected phenotypes and new insights into pathological and molecular mechanisms. Brain 143(1):303-10. doi: 10.1093/brain/awz377 ▪ Méreaux JL et al. (2021) Increasing involvement of CAPN1 variants in spatic ataxias and phenotype-genotype correlations. Neurogenetics 22:71-9. doi: 20.2007/s10048-020-00633-2 ▪ Lallemant-Dudek P & Dürr A (2021) Clinical and genetic update of hereditary spastic paraparesis. Rev Neurol 177(5):550-6. doi: 10.1016/j.neurol.2020.07.001 ▪ Parodi L et al. (2022) The mitochondrial seryl-tRNA synthetase SARS2 modifies onset in spastic paraplegia type 4 (submitted)
Prof. Dr. Dominik Paquet, Institute for Stroke and Dementia Research, Ludwig-Maximilians-Universität München
Elucidating the role of Tau isoform expression in human iPSC-derived Tauopathy models
Finished: The study was to induce latestage disease hallmarks in human stem-cell derived Tauopathy models by mimicking the composition of TAU protein and its environment in an adult human brain. These advanced stem-cell-based human brain tissue models shall become an important resource to study human-specific aspects of brain function and dysfunction, contribute to a better understanding of the molecular disease mechanisms underlying Tauopathies, and provide a new basis for drug development. A CRISPR/Cas9 technology has been developed and successfully applied, cultures of cell lines have been established, assays for phenotypic characterization are now available and immunocytochemistry experiments have started. Preliminary data led to an iAward of the Sanofi Innovation Award Program 2020.The research project was funded with 80,000 € for two years.
Publications: Klimmt J, Dannert A, Paquet D (2020) Neurodegeneration in a dish: advancing human stem-cell-based models of Alzheimer’s disease. Curr Opin Neurobiol 61:96-104. doi: 10.1016/j.conb.2020.01.008 ▪ Weisheit I, Kroeger JA, Malik R, Klimmt J, Crusius D, Dannert A, Dichgans M, Paquet D (2020) Detection of deleterious on-target effects after HDR-mediated CRISPR editing. Cell Rep. 31(8):107689. doi: 10.1016/j.celrep.2020.107689
Dr. Frits Kamp, Biochemistry, Ludwig-Maximilians-Universität, München
Identification of putative gamma-secretase associated steroids and their modulating effects on APP substrate cleavage
Finished: Aims were the identification of high-affinity lipid-binding sites in gamma-secretase and the modulation of gamma-secretase mediated C99-TMD substrate cleavage by neurosteroids. Study design and methods were supposed to deliver new important information about the structure and function of gamma-secretase in order to explain which role lipid changes play in the progression of Alzheimer’s disease. There is now consolidated evidence that both gamma-secretase and its C99 substrate have a cholesterol-binding site. New techniques were established to detect binding of steroids to C99, and certain neurosteroids were found that might dramatically modulate C99 processing by gamma-secretase. Further tests will be carried out. The research project was funded with 60,000 € for two years.
Publications: Kamp F et al. (2018) Bexarotene Binds to the Amyloid Precursor Protein Transmembrane Domain, Alters Its alpha-Helical Conformation, and Inhibits gamma-Secretase Nonselectivity in Liposomes. ACS Chem Neurosci 9(7):1702-13. doi:10.1021/acschemneuro.8b00068 - Junker J et al. (2019) Comparison of Strategies for the Determination of Sterol Sulfates via GC-MS Leading to a Novel Deconjugation-Derivatization Protocol. Molecules 24(13):pii: E2353. doi: 10.3390/molecules24132353 - Götz A et al. (2019) Modulating Hinge Flexibility in the APP Transmembrane Domain Alters gamma-Secretase Cleavage. Biophys J 116(11):2103-20. doi: 10.1016/bpj.2019.04.030
Dr. Johannes Levin, Ludwig-Maximilians-Universität, München
Establishment of a cohort of patients with Down syndrome (Trisomy 21) for imaging and biomarker studies
Finished: Approximately three out of four patients with Down syndrome develop a dementia from the fifth decade of live onwards. The anatomical distribution of pathological alterations are similar to the ones of patients with Alzheimer disease. Aims of the study are to recruit a cohort of patients with Down syndrome, to clinically evaluate them, to determine if these patients show different cerebrospinal fluid and plasma concentations of the soluble protein TREM2, and to test how these differences are associated. After a short delay in recruiting patients progress has been made, a new ambulance has been established and patients care has been further standardized using specialized neuropsychological testing procedures. Yet, building a cohort of patients with Down syndrome was not successful. Part of the study was funded with 65,000 €.
Prof. Dr. Robert Perneczky, Klinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität München
1st International Conference on Brain and Cognitive Reserve in Dementia Disorders
Finished: The high calibre two-day conference at the University of Munich in November 2017 focussed mainly on investigations of the structural and the functional brain mechanismens, which can delay or even prevent dementia onset. Too, research on neuroimaging and biomarkers have been addressed. The aim of the international conference (1) a gain in knowledge and (2) a better network of the leading scientists in this area of research has been achieved. Funding by the Foundation was 40,000 €.
Publication: Perneczky R et al. (2019) Translational research on reserve against neurodegenerative disease: concensus report of the International Conference on Cognitive Reserve in the Dementias and Alzheimer's Association Reserve, Resilience and Protective Factors Professional Interest Area working groups. BMC Medicine 17:47. doi: 10.1186/s12916-019-1283-z