Franzmeier Lab | ISD Research

Research Focus

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.

Publications

Team

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 Neurosciences 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 hiking, practicing yoga, and delving into classic literature.

Anna Dewenter, Postdoc

I obtained a Bachelor’s degree in Cognitive Science from the University of Osnabrück, during which I spent a semester at the University of York (UK). I then earned a research Master’s degree in Cognitive Neuroscience at the Donders Institute for Brain, Cognition, and Behavior in the Netherlands. In October 2019, I joined the ISD and the Graduate School for Systemic Neurosciences. My PhD project focused on structural connectivity alterations in cerebral small vessel disease (SVD) and Alzheimer’s disease. I defended my PhD in December 2022, and since then, I have worked as a Postdoctoral researcher with a focus on Cerebral Amyloid Angiopathy, the most common intersection of cerebrovascular and neurodegenerative diseases. In my free time, I enjoy hiking in the nearby Alps, cycling, and traveling.

Sebastian N. Roemer-Cassiano, 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, Neuroimaging department), and started working as a medical doctor in the neurological intensive care unit of 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 Parkinson diseases in comparison to Alzheimer’s Disease, using advanced, state-of-the-art neuroimaging methods. Outside of the 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.

Lukas Frontzkowski, MD, Clinician Scientist

After finishing my study of medicine in 2021 at the LMU, I worked as a clinician scientist in the department of neurology at the UKE Hamburg. My main research focus is 1) biomarker-driven precision medicine and 2) neuroprotective mechanisms in tauopathies and stroke. Building upon my prior experiences in neuroimaging, I joined the Franzmeier lab in 2024 to establish a processing pipeline for a standardized analysis of PET data in the clinical setting. In my free time I enjoy going to the gym, reading and going out with friends.

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.

Zeyu Zhu, PhD student

After receiving a Bachelor's degree in Clinical Medicine I went on to achieve a Master's degree in Neurology from Shanghai Jiao Tong University, China. In the autumn of 2023, I joined the Franzmeier lab to pursue my PhD. Currently, my research is focused on integrating neuroimaging with omics data to unravel the characteristics of tau accumulation and spreading in Alzheimer’s disease. Outside the lab, I have a great fondness for travel and cooking, and I'm also a big fan of photography.

Julia Pescoller, M.Sc. Psychology student

After completing my B.Sc. in Psychology at the LMU in Munich, I started with my master’s degree in Clinical Psychology and Cognitive Neuroscience with specialization in Neuropsychology at the LMU. In October 2023, I joined the Franzmeier lab for my master’s thesis. In my research project, I investigate the complex association between tau pathology and white matter degeneration in Alzheimer’s disease using imaging data. Outside of the lab, I enjoy meeting friends, playing violoncello, skiing, and reading while drinking a good cup of coffee.

The PI