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                                                  3. Franzmeier Lab

                                                  Nicolai Franzmeier – Alzheimer’s Disease Neuroimaging

                                                  • Research focus
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                                                  • The PI
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                                                  Alzheimer’s disease is characterized by the accumulation of cerebral beta-amyloid (Aβ) and tau pathology, which together cause progressive neurodegeneration and cognitive decline.

                                                  Our overarching goal is to better understand the mechanisms that promote the development and progression of Alzheimer’s disease in order to develop clinically applicable personalized medicine models for predicting patient-specific disease trajectories (e.g. Franzmeier et al., Alzheimers Dement, 2020). To this end, we combine multi-modal neuroimaging methods including positron-emission tomography (PET) and magnetic resonance imaging (MRI) with clinical assessments and genetics in large-scale patient data. 

                                                  A major research focus is the prediction of trans-neuronal tau pathology spread, i.e. the major driver of neurodegeneration and cognitive decline in Alzheimer’s disease. In a translational approach, we combine tau-PET imaging with MRI-based connectomics for modeling connectivity-based tau spreading patterns (e.g. Franzmeier et al., Brain, 2019; Nat Commun, 2020). We have recently established connectivity-based tau spreading models, which allow accurate prediction of future tau spreading patterns on the patient level (Franzmeier et al., Sci Adv, 2020). These prediction models have high clinical utility, as they can be utilized to determine patient-specific endpoints in tau targeting trials which can drastically enhance the sensitivity for detecting treatment effects 
                                                  (see here: https://www.alzforum.org/news/research-news/connectivity-not-proximity-predicts-tau-spread or here: https://www.alzforum.org/news/research-news/individualized-tau-pet-model-outperforms-predictive-power-braak-staging) 
                                                  In ongoing collaborative work, we are extensively validating these tau spreading models across atypical Alzheimer’s disease variants and other neurodegenerative tauopathies.


                                                  Franzmeier et al., Sci Adv, 2020

                                                  For our second major interest, we study mechanisms by which life-style factors and genetic variants (i.e. SNPs) modulate Alzheimer’s disease risk. Here, we found recently that key risk SNPs in the BIN1 gene drive specifically the development of tau pathology (Franzmeier et al., Nat Commun, 2019), whereas carriage of SNPs related to neuronal plasticity (i.e. BDNFVal66Met) can be beneficial and attenuate the effect of Alzheimer’s disease pathology on neurodegeneration and cognitive decline (Franzmeier et al., Mol Neurodeg, 2020). In addition, we have identified protective brain mechanisms that are related to life-style factors (e.g. education) and buffer the effect of Alzheimer’s disease related brain changes on cognitive decline (e.g. Franzmeier et al., Neurology, 2017; Brain, 2018; Alz Res Ther, 2018).

                                                  In summary, our research is motivated by the understanding of brain mechanisms that 1) promote the progression of AD pathology and 2) mechanisms that may help protect individuals from developing dementia despite the presence and progression of AD pathology. As an outlook, we aim to bring together these different lines of research to determine how protective mechanisms, genetics and functional brain networks may modulate the spread and progression of AD pathology and the development of AD-related cognitive impairment.

                                                  Contact:

                                                  Dr. Nicolai Franzmeier

                                                  Phone: +49 89 4400 46162

                                                  E-Mail: nicolai.franzmeier@med.uni-muenchen.de

                                                  Tau Spreadings

                                                  2022

                                                  Coenen M, Kuijf HJ, Huenges Wajer IMC, Duering M, Wolters FJ, Fletcher EF, Maillard PM; Alzheimer's Disease Neuroimaging Initiative, Barkhof F, Barnes J, Benke T, Boomsma JMF, Chen CPLH, Dal-Bianco P, Dewenter A, Enzinger C, Ewers M, Exalto LG, Franzmeier N, Groeneveld O, Hilal S, Hofer E, Koek DL, Maier AB, McCreary CR, Padilla CS, Papma JM, Paterson RW, Pijnenburg YAL, Rubinski A, Schmidt R, Schott JM, Slattery CF, Smith EE, Steketee RME, Sudre CH, van den Berg E, van der Flier WM, Venketasubramanian N, Vernooij MW, Xin X, DeCarli C, Biessels GJ, Biesbroek JM. Strategic white matter hyperintensity locations for cognitive impairment: A multicenter lesion-symptom mapping study in 3525 memory clinic patients. Alzheimers Dement. 2022 Dec 12. doi: 10.1002/alz.12827. Epub ahead of print.

                                                  Biel D, Luan Y, Brendel M, Hager P, Dewenter A, Moscoso A, Otero Svaldi D, Higgins IA, Pontecorvo M, Römer S, Steward A, Rubinski A, Zheng L, Schöll M, Shcherbinin S, Ewers M, Franzmeier N; Alzheimer’s Disease Neuroimaging Initiative. Combining tau-PET and fMRI meta-analyses for patient-centered prediction of cognitive decline in Alzheimer's disease. Alzheimers Res Ther. 2022 Nov 7;14(1):166. doi: 10.1186/s13195-022-01105-5. 

                                                  Steward A, Biel D, Brendel M, Dewenter A, Roemer S, Rubinski A, Luan Y, Dichgans M, Ewers M, Franzmeier N; Alzheimer's Disease Neuroimaging Initiative (ADNI). Functional network segregation is associated with attenuated tau spreading in Alzheimer's disease. Alzheimers Dement. 2022 Nov 25. doi: 10.1002/alz.12867. Epub ahead of print.

                                                  Pichet Binette A, Franzmeier N, Spotorno N, Ewers M, Brendel M, Biel D; Alzheimer’s Disease Neuroimaging Initiative, Strandberg O, Janelidze S, Palmqvist S, Mattsson-Carlgren N, Smith R, Stomrud E, Ossenkoppele R, Hansson O. Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer's disease. Nat Commun. 2022 Nov 4;13(1):6635. 

                                                  Rubinski A, Franzmeier N, Dewenter A, Luan Y, Smith R, Strandberg O, Ossenkoppele R, Dichgans M, Hansson O, Ewers M; Alzheimer’s Disease Neuroimaging Initiative (ADNI). Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer's disease. Alzheimers Res Ther. 2022 Sep 24;14(1):139. 

                                                  Katzdobler S, Nitschmann A, Barthel H, Bischof G, Beyer L, Marek K, Song M, Wagemann O, Palleis C, Weidinger E, Nack A, Fietzek U, Kurz C, Häckert J, Stapf T, Ferschmann C, Scheifele M, Eckenweber F, Biechele G, Franzmeier N, Dewenter A, Schönecker S, Saur D, Schroeter ML, Rumpf JJ, Rullmann M, Schildan A, Patt M, Stephens AW, van Eimeren T, Neumaier B, Drzezga A, Danek A, Classen J, Bürger K, Janowitz D, Rauchmann BS, Stöcklein S, Perneczky R, Schöberl F, Zwergal A, Höglinger GU, Bartenstein P, Villemagne V, Seibyl J, Sabri O, Levin J, Brendel M; German Imaging Initiative for Tauopathies (GII4T). Additive value of [18F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome. Eur J Nucl Med Mol Imaging. 2022 Sep 14. doi: 10.1007/s00259-022-05964-w. Epub ahead of print.

                                                  Vöglein J, Franzmeier N, Morris JC, Dieterich M, McDade E, Simons M, Preische O, Hofmann A, Hassenstab J, Benzinger TL, Fagan A, Noble JM, Berman SB, Graff-Radford NR, Ghetti B, Farlow MR, Chhatwal JP, Salloway S, Xiong C, Karch CM, Cairns N, Perrin RJ, Day G, Martins R, Sanchez-Valle R, Mori H, Shimada H, Ikeuchi T, Suzuki K, Schofield PR, Masters CL, Goate A, Buckles V, Fox NC, Chrem P, Allegri R, Ringman JM, Yakushev I, Laske C, Jucker M, Höglinger G, Bateman RJ, Danek A, Levin J; Dominantly Inherited Alzheimer Network. Pattern and implications of neurological examination findings in autosomal dominant Alzheimer disease. Alzheimers Dement. 2022 May 24. doi: 10.1002/alz.12684. Epub ahead of print.

                                                  Schönecker S, Martinez-Murcia FJ, Rauchmann BS, Franzmeier N, Prix C, Wlasich E, Loosli SV, Bochmann K, Gorriz Saez JM, Laforce R Jr, Ducharme S, Tartaglia MC, Finger E, de Mendonça A, Santana I, Sanchez-Valle R, Moreno F, Sorbi S, Tagliavini F, Borroni B, Otto M, Synofzik M, Galimberti D, Vandenberghe R, van Swieten J, Butler C, Gerhard A, Graff C, Danek A, Rohrer JD, Masellis M, Rowe J, Levin J; Genetic Frontotemporal Dementia Intiative (GENFI). Frequency and Longitudinal Course of Motor Signs In Genetic Frontotemporal Dementia. Neurology. 2022 Aug 10:10.1212/WNL.0000000000200828. doi: 10.1212/WNL.0000000000200828. Epub ahead of print. 

                                                  Frontzkowski L, Ewers M, Brendel M, Biel D, Ossenkoppele R, Hager P, Steward A, Dewenter A, Römer S, Rubinski A, Buerger K, Janowitz D, Binette AP, Smith R, Strandberg O, Carlgren NM, Dichgans M, Hansson O, Franzmeier N. Earlier Alzheimer's disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading. Nat Commun. 2022 Aug 20;13(1):4899. doi: 10.1038/s41467-022-32592-7. 

                                                  Rauchmann BS, Brendel M, Franzmeier N, Trappmann L, Zaganjori M, Ersoezlue E, Morenas-Rodriguez E, Guersel S, Burow L, Kurz C, Haeckert J, Tatò M, Utecht J, Papazov B, Pogarell O, Janowitz D, Buerger K, Ewers M, Palleis C, Weidinger E, Biechele G, Schuster S, Finze A, Eckenweber F, Rupprecht R, Rominger A, Goldhardt O, Grimmer T, Keeser D, Stoecklein S, Dietrich O, Bartenstein P, Levin J, Höglinger G, Perneczky R. Microglial Activation and Connectivity in Alzheimer Disease and Aging. Ann Neurol. 2022 Aug 1. doi: 10.1002/ana.26465. Epub ahead of print. 

                                                  Dewenter A, Jacob MA, Cai M, Gesierich B, Hager P, Kopczak A, Biel D, Ewers M, Tuladhar AM, de Leeuw FE, Dichgans M, Franzmeier N, Duering M; SVDs@target Consortium and Alzheimer’s Disease Neuroimaging Initiative (ADNI). Disentangling the effects of Alzheimer's and small vessel disease on white matter fibre tracts. Brain. 2022 Jul 21:awac265. doi: 10.1093/brain/awac265. Epub ahead of print. 

                                                  Franzmeier N, Höglinger GU. Inferring the sequence of brain volume changes in progressive supranuclear palsy using MRI. Brain Commun. 2022 May 12;4(3):fcac113. doi: 10.1093/braincomms/fcac113. 

                                                  Vöglein J, Franzmeier N, Morris JC, Dieterich M, McDade E, Simons M, Preische O, Hofmann A, Hassenstab J, Benzinger TL, Fagan A, Noble JM, Berman SB, Graff-Radford NR, Ghetti B, Farlow MR, Chhatwal JP, Salloway S, Xiong C, Karch CM, Cairns N, Perrin RJ, Day G, Martins R, Sanchez-Valle R, Mori H, Shimada H, Ikeuchi T, Suzuki K, Schofield PR, Masters CL, Goate A, Buckles V, Fox NC, Chrem P, Allegri R, Ringman JM, Yakushev I, Laske C, Jucker M, Höglinger G, Bateman RJ, Danek A, Levin J; Dominantly Inherited Alzheimer Network. Patterns and implications of neurological examination findings in autosomal dominant Alzheimer disease. Alzheimers Dement. 2022 May 24. doi: 10.1002/alz.12684. Epub ahead of print. PMID: 35609137.

                                                  Blume T, Deussing M, Biechele G, Peters F, Zott B, Schmidt C, Franzmeier N, Wind K, Eckenweber F, Sacher C, Shi Y, Ochs K, Kleinberger G, Xiang X, Focke C, Lindner S, Gildehaus FJ, Beyer L, von Ungern-Sternberg B, Bartenstein P, Baumann K, Adelsberger H, Rominger A, Cumming P, Willem M, Dorostkar MM, Herms J, Brendel M. Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition. Front Aging Neurosci. 2022 Mar 30;14:854031. doi: 10.3389/fnagi.2022.854031. 

                                                  Morenas-Rodríguez E, Li Y, Nuscher B, Franzmeier N, Xiong C, Suárez-Calvet M, Fagan AM, Schultz S, Gordon BA, Benzinger TLS, Hassenstab J, McDade E, Feederle R, Karch CM, Schlepckow K, Morris JC, Kleinberger G, Nellgard B, Vöglein J, Blennow K, Zetterberg H, Ewers M, Jucker M, Levin J, Bateman RJ, Haass C; Dominantly Inherited Alzheimer Network. Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer's disease: a longitudinal observational study. Lancet Neurol. 2022 Apr;21(4):329-341. doi: 10.1016/S1474-4422(22)00027-8. 

                                                  Franzmeier N, Brendel M, Beyer L, Slemann L, Kovacs GG, Arzberger T, Kurz C, Respondek G, Lukic MJ, Biel D, Rubinski A, Frontzkowski L, Hummel S, Müller A, Finze A, Palleis C, Joseph E, Weidinger E, Katzdobler S, Song M, Biechele G, Kern M, Scheifele M, Rauchmann BS, Perneczky R, Rullman M, Patt M, Schildan A, Barthel H, Sabri O, Rumpf JJ, Schroeter ML, Classen J, Villemagne V, Seibyl J, Stephens AW, Lee EB, Coughlin DG, Giese A, Grossman M, McMillan CT, Gelpi E, Molina-Porcel L, Compta Y, van Swieten JC, Laat LD, Troakes C, Al-Sarraj S, Robinson JL, Xie SX, Irwin DJ, Roeber S, Herms J, Simons M, Bartenstein P, Lee VM, Trojanowski JQ, Levin J, Höglinger G, Ewers M. Tau deposition patterns are associated with functional connectivity in primary tauopathies. Nat Commun. 2022 Mar 15;13(1):1362. doi: 10.1038/s41467-022-28896-3. 

                                                  2021

                                                  Dewenter A, Gesierich B, Ter Telgte A, Wiegertjes K, Cai M, Jacob MA, Marques JP, Norris DG, Franzmeier N, de Leeuw FE, Tuladhar AM, Duering M. Systematic validation of structural brain networks in cerebral small vessel disease. J Cereb Blood Flow Metab. 2021 Dec 20:271678X211069228. doi: 10.1177/0271678X211069228. Epub ahead of print. 

                                                  Biechele G, Blume T, Deussing M, Zott B, Shi Y, Xiang X, Franzmeier N, Kleinberger G, Peters F, Ochs K, Focke C, Sacher C, Wind K, Schmidt C, Lindner S, Gildehaus FJ, Eckenweber F, Beyer L, von Ungern-Sternberg B, Bartenstein P, Baumann K, Dorostkar MM, Rominger A, Cumming P, Willem M, Adelsberger H, Herms J, Brendel M. Pre-therapeutic microglia activation and sex determine therapy effects of chronic immunomodulation. Theranostics. 2021 Aug 19;11(18):8964-8976. doi: 10.7150/thno.64022. PMID: 34522221; PMCID: PMC8419052.

                                                  Xiang X, Wind K, Wiedemann T, Blume T, Shi Y, Briel N, Beyer L, Biechele G, Eckenweber F, Zatcepin A, Lammich S, Ribicic S, Tahirovic S, Willem M, Deussing M, Palleis C, Rauchmann BS, Gildehaus FJ, Lindner S, Spitz C, Franzmeier N, Baumann K, Rominger A, Bartenstein P, Ziegler S, Drzezga A, Respondek G, Buerger K, Perneczky R, Levin J, Höglinger GU, Herms J, Haass C, Brendel M. Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases. Sci Transl Med. 2021 Oct 13;13(615):eabe5640. doi: 10.1126/scitranslmed.abe5640. Epub 2021 Oct 13. PMID: 34644146.

                                                  Biel D, Brendel M, Rubinski A, Buerger K, Janowitz D, Dichgans M, Franzmeier N; Alzheimer’s Disease Neuroimaging Initiative (ADNI). Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals. Alzheimers Res Ther. 2021 Aug 12;13(1):137. doi: 10.1186/s13195-021-00880-x. PMID: 34384484.

                                                  Neitzel J, Franzmeier N, Rubinski A, Dichgans M, Brendel M; Alzheimer’s Disease Neuroimaging Initiative (ADNI), Malik R, Ewers M. KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer's disease. Nat Commun. 2021 Jun 22;12(1):3825. doi: 10.1038/s41467-021-23755-z. PMID: 34158479.

                                                  Franzmeier N, Ossenkoppele R, Brendel M, Rubinski A, Smith R, Kumar A, Mattsson-Carlgren N, Strandberg O, Duering M, Buerger K, Dichgans M, Hansson O, Ewers M; Alzheimer's Disease Neuroimaging Initiative (ADNI)* and the Swedish BioFINDER study. The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline. Alzheimers Dement. 2021 Jun 1. doi: 10.1002/alz.12371. Epub ahead of print.

                                                  Heindl S, Ricci A, Carofiglio O, Zhou Q, Arzberger T, Lenart N, Franzmeier N, Hortobagyi T, Nelson PT, Stowe AM, Denes A, Edbauer D, Liesz A. Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies. J Exp Med. 2021 Aug 2;218(8):e20202411. 

                                                  Rubinski A, Tosun D, Franzmeier N, Neitzel J, Frontzkowski L, Weiner M, Ewers M. Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex across the Alzheimer's continuum. Neurobiol Aging. 2021 Feb 10;102:111-118. doi: 10.1016/j.neurobiolaging.2021.02.003. Epub ahead of print. 

                                                  Ewers M, Luan Y, Frontzkowski L, Neitzel J, Rubinski A, Dichgans M, Hassenstab J, Gordon BA, Chhatwal JP, Levin J, Schofield P, Benzinger TLS, Morris JC, Goate A, Karch CM, Fagan AM, McDade E, Allegri R, Berman S, Chui H, Cruchaga C, Farlow M, Graff-Radford N, Jucker M, Lee JH, Martins RN, Mori H, Perrin R, Xiong C, Rossor M, Fox NC, O'Connor A, Salloway S, Danek A, Buerger K, Bateman RJ, Habeck C, Stern Y, Franzmeier N; Alzheimer’s Disease Neuroimaging Initiative and the Dominantly Inherited Alzheimer Network. Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease. Brain. 2021 Mar 16:awab112. doi: 10.1093/brain/awab112. Epub ahead of print. 

                                                  2020

                                                  Biechele G, Wind K, Blume T, Sacher C, Beyer L, Eckenweber F, Franzmeier N, Ewers M, Zott B, Lindner S, Gildehaus FJ, von Ungern-Sternberg B, Tahirovic S, Willem M, Bartenstein P, Cumming P, Rominger A, Herms J, Brendel M. Microglial Activation in the Right Amygdala-Entorhinal-Hippocampal Complex is Associated with Preserved Spatial Learning in AppNL-G-F mice. Neuroimage. 2020 Dec 29:117707. doi: 10.1016/j.neuroimage.2020.117707. Epub ahead of print. 

                                                  Biechele G, Franzmeier N, Blume T, Ewers M, Luque JM, Eckenweber F, Sacher C, Beyer L, Ruch-Rubinstein F, Lindner S, Gildehaus FJ, von Ungern-Sternberg B, Cumming P, Bartenstein P, Rominger A, Höglinger GU, Herms J, Brendel M. Glial activation is moderated by sex in response to amyloidosis but not to tau pathology in mouse models of neurodegenerative diseases. J Neuroinflammation. 2020 Dec 14;17(1):374. 

                                                  Bartrés-Faz D, Arenaza-Urquijo E, Ewers M, Belleville S, Chételat G, Franzmeier N, Gonneaud J, de Echevarri JMG, Okonkwo O, Schultz S, Valenzuela M, Stern Y, Vemuri P. Theoretical frameworks and approaches used within the Reserve, Resilience and Protective Factors professional interest area of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment. Alzheimers Dement (Amst). 2020 Nov 11;12(1):e12115. 

                                                  Franzmeier N, Dewenter A, Frontzkowski L, Dichgans M, Rubinski A, Neitzel J, Smith R, Strandberg O, Ossenkoppele R, Buerger K, Duering M, Hansson O, Ewers M. Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer's disease. Sci Adv. 2020 Nov 27;6(48):eabd1327. 

                                                  Rubinski A, Franzmeier N, Neitzel J, Ewers M; Alzheimer’s Disease Neuroimaging Initiative (ADNI). FDG-PET hypermetabolism is associated with higher tau-PET in mild cognitive impairment at low amyloid-PET levels. Alzheimers Res Ther. 2020 Oct 19;12(1):133. 

                                                  Franzmeier N, Suárez-Calvet M, Frontzkowski L, Moore A, Hohman TJ, Morenas-Rodriguez E, Nuscher B, Shaw L, Trojanowski JQ, Dichgans M, Kleinberger G, Haass C, Ewers M; Alzheimer’s Disease Neuroimaging Initiative (ADNI). Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration. Mol Neurodegener. 2020 Oct 8;15(1):57. 

                                                  Finsterwalder S, Vlegels N, Gesierich B, Araque Caballero MÁ, Weaver NA, Franzmeier N, Georgakis MK, Konieczny MJ, Koek HL; Dominantly Inherited Alzheimer Network (DIAN), Karch CM, Graff-Radford NR, Salloway S, Oh H, Allegri RF, Chhatwal JP; DELCODE study group, Jessen F, Düzel E, Dobisch L, Metzger C, Peters O, Incesoy EI, Priller J, Spruth EJ, Schneider A, Fließbach K, Buerger K, Janowitz D, Teipel SJ, Kilimann I, Laske C, Buchmann M, Heneka MT, Brosseron F, Spottke A, Roy N, Ertl-Wagner B, Scheffler K; Alzheimer's Disease Neuroimaging Initiative (ADNI); Utrecht VCI study group, Seo SW, Kim Y, Na DL, Kim HJ, Jang H, Ewers M, Levin J, Schmidt R, Pasternak O, Dichgans M, Biessels GJ, Duering M. Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients. Alzheimers Dement. 2020 Nov;16(11):1504-1514. 

                                                  Ewers M, Biechele G, Suárez-Calvet M, Sacher C, Blume T, Morenas-Rodriguez E, Deming Y, Piccio L, Cruchaga C, Kleinberger G, Shaw L, Trojanowski JQ, Herms J, Dichgans M; Alzheimer's Disease Neuroimaging Initiative (ADNI), Brendel M, Haass C, Franzmeier N. Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation. EMBO Mol Med. 2020 Sep 7;12(9):e12308. 

                                                  Gürsel DA, Reinholz L, Bremer B, Schmitz-Koep B, Franzmeier N, Avram M, Koch K. Frontoparietal and salience network alterations in obsessive–compulsive disorder: insights from independent component and sliding time window analyses. J Psychiatry Neurosci. 2020 May 1;45(3):214-221. 

                                                  Gesierich B, Tuladhar AM, Ter Telgte A, Wiegertjes K, Konieczny MJ, Finsterwalder S, Hübner M, Pirpamer L, Koini M, Abdulkadir A, Franzmeier N, Norris DG, Marques JP, Zu Eulenburg P, Ewers M, Schmidt R, de Leeuw FE, Duering M. Alterations and test-retest reliability of functional connectivity network measures in cerebral small vessel disease. Hum Brain Mapp. 2020 Jul;41(10):2629-2641. 

                                                  Franzmeier N, Koutsouleris N, Benzinger T, Goate A, Karch CM, Fagan AM, McDade E, Duering M, Dichgans M, Levin J, Gordon BA, Lim YY, Masters CL, Rossor M, Fox NC, O'Connor A, Chhatwal J, Salloway S, Danek A, Hassenstab J, Schofield PR, Morris JC, Bateman RJ; Alzheimer's disease neuroimaging initiative (ADNI); Dominantly Inherited Alzheimer Network (DIAN), Ewers M. Predicting sporadic Alzheimer's disease progression via inherited Alzheimer's disease-informed machine-learning. Alzheimers Dement. 2020 Mar;16(3):501-511. 

                                                  Franzmeier N, Neitzel J, Rubinski A, Smith R, Strandberg O, Ossenkoppele R, Hansson O, Ewers M; Alzheimer’s Disease Neuroimaging Initiative (ADNI). Functional brain architecture is associated with the rate of tau accumulation in Alzheimer's disease. Nat Commun. 2020 Jan 17;11(1):347. 

                                                  Stern Y, Arenaza-Urquijo EM, Bartrés-Faz D, Belleville S, Cantilon M, Chetelat G, Ewers M, Franzmeier N, Kempermann G, Kremen WS, Okonkwo O, Scarmeas N, Soldan A, Udeh-Momoh C, Valenzuela M, Vemuri P, Vuoksimaa E; the Reserve, Resilience and Protective Factors PIA Empirical Definitions and Conceptual Frameworks Workgroup. Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement. 2020 Sep;16(9):1305-1311. 

                                                  Franzmeier N, Koutsouleris N, Benzinger T, Goate A, Karch CM, Fagan AM, McDade E, Duering M, Dichgans M, Levin J, Gordon BA, Lim YY, Masters CL, Rossor M, Fox NC, O'Connor A, Chhatwal J, Salloway S, Danek A, Hassenstab J, Schofield PR, Morris JC, Bateman RJ; Alzheimer's disease neuroimaging initiative (ADNI); Dominantly Inherited Alzheimer Network (DIAN), Ewers M. Predicting sporadic Alzheimer's disease progression via inherited Alzheimer's disease-informed machine-learning. Alzheimers Dement. 2020 Mar;16(3):501-511.

                                                  2019

                                                  Ewers M, Franzmeier N, Suárez-Calvet M, Morenas-Rodriguez E, Caballero MAA, Kleinberger G, Piccio L, Cruchaga C, Deming Y, Dichgans M, Trojanowski JQ, Shaw LM, Weiner MW, Haass C; Alzheimer’s Disease Neuroimaging Initiative. Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease. Sci Transl Med. 2019 Aug 28;11(507).

                                                  Bischof GN, Ewers M, Franzmeier N, Grothe MJ, Hoenig M, Kocagoncu E, Neitzel J, Rowe JB, Strafella A, Drzezga A, van Eimeren T; MINC faculty. Connectomics and molecular imaging in neurodegeneration. Eur J Nucl Med Mol Imaging. 2019 Dec;46(13):2819-2830. doi: 10.1007/s00259-019-04394-5. Epub 2019 Jul 11. PMID: 31292699.

                                                  Neitzel J, Franzmeier N, Rubinski A, Ewers M; Alzheimer's Disease Neuroimaging Initiative (ADNI). Left frontal connectivity attenuates the adverse effect of entorhinal tau pathology on memory. Neurology. 2019 Jul 23;93(4):e347-e357. 

                                                  Franzmeier N, Rubinski A, Neitzel J, Ewers M; Alzheimer’s Disease Neuroimaging Initiative (ADNI). The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory. Nat Commun. 2019 Apr 16;10(1):1766. 

                                                  Franzmeier N, Rubinski A, Neitzel J, Kim Y, Damm A, Na DL, Kim HJ, Lyoo CH, Cho H, Finsterwalder S, Duering M, Seo SW, Ewers M; Alzheimer’s Disease Neuroimaging Initiative. Functional connectivity associated with tau levels in ageing, Alzheimer's, and small vessel disease. Brain. 2019 Apr 1;142(4):1093-1107. 

                                                  Franzmeier N, Ren J, Damm A, Monté-Rubio G, Boada M, Ruiz A, Ramirez A, Jessen F, Düzel E, Rodríguez Gómez O, Benzinger T, Goate A, Karch CM, Fagan AM, McDade E, Buerger K, Levin J, Duering M, Dichgans M, Suárez-Calvet M, Haass C, Gordon BA, Lim YY, Masters CL, Janowitz D, Catak C, Wolfsgruber S, Wagner M, Milz E, Moreno-Grau S, Teipel S, Grothe MJ, Kilimann I, Rossor M, Fox N, Laske C, Chhatwal J, Falkai P, Perneczky R, Lee JH, Spottke A, Boecker H, Brosseron F, Fliessbach K, Heneka MT, Nestor P, Peters O, Fuentes M, Menne F, Priller J, Spruth EJ, Franke C, Schneider A, Westerteicher C, Speck O, Wiltfang J, Bartels C, Araque Caballero MÁ, Metzger C, Bittner D, Salloway S, Danek A, Hassenstab J, Yakushev I, Schofield PR, Morris JC, Bateman RJ, Ewers M. The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer's disease. Mol Psychiatry. 2019 Mar 21. 

                                                  Suárez-Calvet M, Morenas-Rodríguez E, Kleinberger G, Schlepckow K, Araque Caballero MÁ, Franzmeier N, Capell A, Fellerer K, Nuscher B, Eren E, Levin J, Deming Y, Piccio L, Karch CM, Cruchaga C, Shaw LM, Trojanowski JQ, Weiner M, Ewers M, Haass C; Alzheimer’s Disease Neuroimaging Initiative. Early increase of CSF sTREM2 in Alzheimer's disease is associated with tau related-neurodegeneration but not with amyloid-β pathology. Mol Neurodegener. 2019 Jan 10;14(1):1. 

                                                  2018

                                                  Suárez-Calvet M, Capell A, Araque Caballero MÁ, Morenas-Rodríguez E, Fellerer K, Franzmeier N, Kleinberger G, Eren E, Deming Y, Piccio L, Karch CM, Cruchaga C, Paumier K, Bateman RJ, Fagan AM, Morris JC, Levin J, Danek A, Jucker M, Masters CL, Rossor MN, Ringman JM, Shaw LM, Trojanowski JQ, Weiner M, Ewers M, Haass C; Dominantly Inherited Alzheimer Network; Alzheimer's Disease Neuroimaging Initiative. CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline. EMBO Mol Med. 2018 Dec;10(12):e9712. 

                                                  Simon-Vermot L, Taylor ANW, Araque Caballero MÀ, Franzmeier N, Buerger K, Catak C, Janowitz D, Kambeitz-Ilankovic LM, Ertl-Wagner B, Duering M, Ewers M. Correspondence Between Resting-State and Episodic Memory-Task Related Networks in Elderly Subjects. Front Aging Neurosci. 2018 Nov 8;10:362. 

                                                  Araque Caballero MÁ, Suárez-Calvet M, Duering M, Franzmeier N, Benzinger T, Fagan AM, Bateman RJ, Jack CR, Levin J, Dichgans M, Jucker M, Karch C, Masters CL, Morris JC, Weiner M, Rossor M, Fox NC, Lee JH, Salloway S, Danek A, Goate A, Yakushev I, Hassenstab J, Schofield PR, Haass C, Ewers M. White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer's disease. Brain. 2018 Oct 1;141(10):3065-3080. 

                                                  Franzmeier N, Düzel E, Jessen F, Buerger K, Levin J, Duering M, Dichgans M, Haass C, Suárez-Calvet M, Fagan AM, Paumier K, Benzinger T, Masters CL, Morris JC, Perneczky R, Janowitz D, Catak C, Wolfsgruber S, Wagner M, Teipel S, Kilimann I, Ramirez A, Rossor M, Jucker M, Chhatwal J, Spottke A, Boecker H, Brosseron F, Falkai P, Fliessbach K, Heneka MT, Laske C, Nestor P, Peters O, Fuentes M, Menne F, Priller J, Spruth EJ, Franke C, Schneider A, Kofler B, Westerteicher C, Speck O, Wiltfang J, Bartels C, Araque Caballero MÁ, Metzger C, Bittner D, Weiner M, Lee JH, Salloway S, Danek A, Goate A, Schofield PR, Bateman RJ, Ewers M. Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease. Brain. 2018 Apr 1;141(4):1186-1200. 

                                                  Franzmeier N, Hartmann J, Taylor ANW, Araque-Caballero MÁ, Simon-Vermot L, Kambeitz-Ilankovic L, Bürger K, Catak C, Janowitz D, Müller C, Ertl-Wagner B, Stahl R, Dichgans M, Duering M, Ewers M. The left frontal cortex supports reserve in aging by enhancing functional network efficiency. Alzheimers Res Ther. 2018 Mar 6;10(1):28. 

                                                  2017

                                                  Franzmeier N, Dyrba M. Functional brain network architecture may route progression of Alzheimer's disease pathology. Brain. 2017 Dec 1;140(12):3077-3080. 

                                                  Franzmeier N, Göttler J, Grimmer T, Drzezga A, Áraque-Caballero MA, Simon-Vermot L, Taylor ANW, Bürger K, Catak C, Janowitz D, Müller C, Duering M, Sorg C, Ewers M. Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment. Front Aging Neurosci. 2017 Aug 7;9:264. 

                                                  Franzmeier N, Caballero MÁA, Taylor ANW, Simon-Vermot L, Buerger K, Ertl-Wagner B, Mueller C, Catak C, Janowitz D, Baykara E, Gesierich B, Duering M, Ewers M; Alzheimer’s Disease Neuroimaging Initiative. Resting-state global functional connectivity as a biomarker of cognitive reserve in mild cognitive impairment. Brain Imaging Behav. 2017 Apr;11(2):368-382. 

                                                  Franzmeier N, Duering M, Weiner M, Dichgans M, Ewers M; Alzheimer's Disease Neuroimaging Initiative (ADNI). Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease. Neurology. 2017 Mar 14;88(11):1054-1061. 

                                                  Teipel SJ, Grothe MJ, Metzger CD, Grimmer T, Sorg C, Ewers M, Franzmeier N, Meisenzahl E, Klöppel S, Borchardt V, Walter M, Dyrba M. Robust Detection of Impaired Resting State Functional Connectivity Networks in Alzheimer's Disease Using Elastic Net Regularized Regression. Front Aging Neurosci. 2017 Jan 4;8:318. 

                                                  Franzmeier N, Hartmann JC, Taylor ANW, Araque Caballero MÁ, Simon-Vermot L, Buerger K, Kambeitz-Ilankovic LM, Ertl-Wagner B, Mueller C, Catak C, Janowitz D, Stahl R, Dichgans M, Duering M, Ewers M. Left Frontal Hub Connectivity during Memory Performance Supports Reserve in Aging and Mild Cognitive Impairment. J Alzheimers Dis. 2017;59(4):1381-1392. 
                                                  Franzmeier N, Buerger K, Teipel S, Stern Y, Dichgans M, Ewers M; Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive reserve moderates the association between functional network anti-correlations and memory in MCI. Neurobiol Aging. 2017 Feb;50:152-162. 

                                                  Taylor ANW, Kambeitz-Ilankovic L, Gesierich B, Simon-Vermot L, Franzmeier N, Araque Caballero MÁ, Müller S, Hesheng L, Ertl-Wagner B, Bürger K, Weiner MW, Dichgans M, Duering M, Ewers M; Alzheimer's Disease Neuroimaging Initiative (ADNI). Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer's disease. Alzheimers Dement. 2017 Mar;13(3):225-235. 

                                                  Niko Franzmeier

                                                  Nicolai Franzmeier, Principal Investigator

                                                  I am an early career investigator with a strong focus on Alzheimer’s disease (AD) neuroimaging research. I received undergraduate training in psychology and medicine from 2009-2014 in Innsbruck, Austria, after which I completed my PhD at the graduate school for systemic neurosciences (LMU) in Munich in 2017. I am specifically interested in the 1) spatiotemporal evolution of AD-related brain changes that underlie cognitive decline and 2) those factors that provide resilience in AD. My overall goal is to develop clinically useful models for predicting disease progression and to identify therapeutically relevant targets for secondary prevention of AD dementia. To this end, I am combining structural & functional MRI with molecular PET imaging and genetics. (Please read about CV on the next tab.)

                                                  Davina Biel

                                                  Davina Biel, Postdoc

                                                  I received undergraduate training in psychology and neuroscience from the University of Bremen, including lab rotations in Barcelona and Melbourne. Afterwards I moved to Lübeck to start my PhD in Neuroscience, focusing cognitive training effects and structural brain changes in older adults. I graduated in September 2020 and since then join the ISD as a post-doc in Munich focusing on neuroimaging in Alzheimer’s disease. I am interested in mechanisms of tau-spreading, genetics, and health factors which help to understand the progression in Alzheimer’s disease and facilitate patient-specific risk prediction. Outside the lab, I like to spend my time outdoors, go bouldering, or read old Russian literature.

                                                  Anna Dewenter 

                                                  Anna Dewenter, PhD student

                                                  I obtained a Bachelor’s degree in Cognitive Science at the University of Osnabrück, during which I spent a semester at the University of York (UK), and a research Master’s degree in Cognitive Neuroscience at the Donders Institute for Brain, Cognition and Behaviour (NL). In October 2019, I joined the ISD and the Graduate School for Systemic Neurosciences. My PhD project focusses on structural connectivity in cerebral small vessel disease (SVD) and the intersection between SVD and Alzheimer’s disease. As such, I am co-supervised by Prof. Marco Düring and Dr. Nicolai Franzmeier. In my free time, I enjoy hiking in the close-by Alps, cycling and travelling.

                                                  Sebastian Römer, Clinician Scientist 

                                                  After receiving my Bachelor‘s degree in human and molecular biology at the University of Freiburg and Saarland, I went on studying Medicine at the University of Saarland. I am currently working on my doctoral thesis at the university clinic of the Technical University Munich (TUM, Neuroimmaging department), and started working as a medical doctor in the neurological intensive care unit oft the university clinic Munich (LMU, neurology). In August 2021 I joined the lab of Nicolai Franzmeier at ISD, trying to shed light on the pathophysiology of atypical parkisnon diseases in comparison to Alzheimer’s Disease, using advanced, state-of-the-art neuroimmaging methods. Outside oft he lab I enjoy meeting friends, travelling, playing volleyball, Ping-Pong and Chess.

                                                  Amir Dehsarvi, PhD

                                                  My research focuses on the application of machine learning/deep learning for the analysis of biomedical (brain imaging, movement, speech, etc.) data for disease diagnosis/target identification and validation (Parkinson’s disease, Alzheimer’s disease, autism, depression, rheumatoid arthritis, etc.), using diverse types of large, complex, biomedical datasets (e.g., brain imaging, movement, and speech), in which I lead the development of novel end-to-end analyses. I joined ISD as a postdoctoral researcher to continue my research career in March 2022. Here, I mainly work on developing cutting-edge preprocessing and processing techniques for different image modalities. Prior to this, I received my BSc in applied science electronics in Iran, and I completed a MSc in digital signal processing, followed by a PhD in electronic engineering at the University of York, UK. Subsequently, I have been working within various research positions at the University of York (England), the University of Aberdeen (Scotland), and at Trinity College Dublin (Ireland), in addition to working in various diverse biomedical companies (Spain, England, and the USA). In my spare time, I am an avid film enthusiast and I collect music, I play the Setar (a traditional Iranian instrument), and I enjoy hiking and cycling in the nature.

                                                  Anna Steward, PhD student

                                                  After achieving a BSc in Psychology I went on to obtain an MSc in Cognitive Neuroscience from the University of York, UK. My main research focus was in the field of semantic cognition in which I investigated the interactions of major cortical networks responsible for flexible semantic retrieval using functional magnetic resonance imaging. Now, at the ISD, my research focuses on functional connectivity in Alzheimer's disease and its influence on the spread of amyloid beta and tau pathologies. Outside of work I am a keen hiker, skier and cook

                                                  Hannah De Bruin, PhD Student

                                                  I obtained a Bachelor’s degree in Psychology at the VU Amsterdam, with a specialization in Biological- and Neuropsychology. Within this program, I got the opportunity to spend a semester at the University at Buffalo in New York State (USA). While taking several neuroscience courses, I developed a strong interest in the complex mechanisms of the human brain and went on to obtain both a two-year Research Master in Neurosciences in Amsterdam as well as a clinical Master’s degree in Neuropsychology. After graduation, I worked as a neuropsychologist in a nursing home for a year, and in June of 2022 I started my PhD in a cross-border research project in the labs of Dr. Nicolai Franzmeier at the ISD and in Dr. Rik Ossenkoppele’s lab at the Alzheimer Center Amsterdam. In my PhD-project, we explore functional connectivity as a predictor of tau spreading in atypical variants of Alzheimer’s disease by combining PET and Post-Mortem data. I am doing my PhD part-time, as I carry on with my work as a neuropsychologist for one day a week. In my leisure time, I like to meet with friends, watch movies, go swimming, travel, and cuddle with my cats.

                                                  Fabian Wagner, MD doctoral student

                                                  After growing up near the city of Linz in Austria, I have been studying medicine at the LMU since fall 2018. In the summer of 2022, I joined Franzmeier lab for my MD-Thesis. I am investigating the complex interplay between Beta-Amyloid and Tau in Alzheimer’s disease using imaging data. In my spare time I participate in extracurricular student groups, play guitar and attend language courses.

                                                  Mattes Groß

                                                  Nicolai Franzmeier

                                                  Nicolai Franzmeier, Principal investigator

                                                  PI data sheet:

                                                  I am an early career investigator with a strong focus on Alzheimer’s disease (AD) neuroimaging research. I received undergraduate training in psychology and medicine from 2009-2014 in Innsbruck, Austria, after which I completed my PhD at the graduate school for systemic neurosciences (LMU) in Munich in 2017. I am specifically interested in the 1) spatiotemporal evolution of AD-related brain changes that underlie cognitive decline and 2) those factors that provide resilience in AD. My overall goal is to develop clinically useful models for predicting disease progression and to identify therapeutically relevant targets for secondary prevention of AD dementia. To this end, I am combining structural & functional MRI with molecular PET imaging and genetics.

                                                  Personal Data:

                                                  Nicolai Franzmeier, PhD

                                                  Date of birth: 05 April 1989

                                                  Place of birth: Munich

                                                  Junior Research Group Leader

                                                  Institute for Stroke and Dementia Research

                                                  Ludwig-Maximilians-University (LMU), Munich

                                                  Scientific vita:

                                                  Since 2021: Junior Research Group Leader, Institute for Stroke and Dementia Research, LMU Hospital

                                                  2017-2020: Post-doctoral researcher, Institute for Stroke and Dementia Research, LMU Hospital, Ludwig-Maximilians University, Munich

                                                  2014-2017: PhD, Graduate School for Systemic Neurosciences, Institute for Strike and Dementia Research, LMU Hospital, Ludwig-Maximilians University, Munich

                                                  Coordinating functions, honors and Awards:

                                                  2022: Helga Freyberg Rüßmann Award for Medical Research 

                                                  2020: Bayer Early Excellence in Science Award

                                                  Since 2019: Vice-Chair: Reserve, Resilience and Protective Factors Professional Interest Area (PIA), ISTAART, Alzheimer’s Association

                                                  2017-2019: Programs Chair: Reserve, Resilience and Protective Factors Professional Interest Area (PIA), ISTAART, Alzheimer’s Association

                                                  2017: Steinberg-Krupp Alzheimer Research Award

                                                  Funding:

                                                  We gratefully acknowledge funding by the following funding agencies:

                                                  Alzheimer’s Association

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                                                  LMUexcellent

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                                                  Alzheimer Forschung Initiative eV

                                                  Die Alzheimer Forschung Initiative e.V.

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                                                  Bright-Focus Foundation

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                                                  Gemeinnützige Hertie Stiftung

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                                                  FöFoLe

                                                  Excellence program for research and funding (FöFoLe, LMU)

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                                                  Institute for Stroke and Dementia Research (ISD)
                                                  University Hospital, LMU Munich

                                                  Director: Prof. Dr. med. Martin Dichgans

                                                  Feodor-Lynen-Straße 17
                                                  81377 Munich, Germany

                                                  Phone: +49 (0)89 4400 46019
                                                  www.isd-research.de
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