Nicolai Franzmeier – Alzheimer’s Disease Neuroimaging
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.
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.
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.
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.
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.
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, 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.
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.
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).
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.
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.
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, 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, 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.
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.
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.
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
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
We gratefully acknowledge funding by the following funding agencies: