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Research Focus

Our research focuses on the spreading of key pathologies in Alzheimer’s disease (AD) and the improvement of prediction tools. Specifically, we combine functional connectomics, myelin imaging and advanced molecular PET markers to model the spatiotemporal evolution of fibrillar tau and beta-amyloid. Our prediction models are tailored to enable precision-medicine guided patient-level prognosis of disease progression. Another research focus of our team centers on brain mechanisms underlying cognitive resilience in AD. Specifically, we examine the protective factors of the brain’s innate immune system along with functional network changes that alleviate cognitive decline.

Functional connectome & progression of tau pathology

Neurofibrillar tangles are the single most important drivers of neurodegeneration and cognitive decline in AD. The tau-bearing tangle deposits progress in spatiotemporally distinct patterns in the brain, but which factors shape that spatial distribution is unclear. Based on joined resting-state fMRI connectivity and tau PET analysis, we found that fibrillar tau accumulation progresses from initial epicenters of high tau to those brain areas that are most closely connected to the epicenter. Our approach allows to predict the progression of tau accumulation at the patient-level, thus providing an important step towards precision medicine.

Functional networks supporting cognitive resilience

Cognitive resilience designates the ability to show disproportional high levels of cognitive function despite substantial brain pathology. Cognitive resilience is an important factor slowing down the development of dementia in AD, but the underlying mechanism are not well understood. To address that question, we focus on the topological characteristics of the functional connectome of the brain that underly resilience. Using graph theoretical analyses, we identified hub connectivity in the fronto-parietal control network (Neitzel et al. 2019) as well as higher segregation of functional networks (Franzmeier et al. Brain, in press) as key neural substrates supporting cognitive resilience against pathologic tau.

The role of TREM2-related microglia activation in Alzheimer’s

Rare loss-of-function mutations in the gene encoding TREM2, i.e. a receptor molecular expressed by microglia, are associated with a dramatic increase in the risk of AD. Together with our collaborator Prof. Christian Haass (DZNE, Munich), we found changes in biofluid levels of soluble TREM2 protein occur up to 5 years before the onset of AD dementia (Suarez-Calvet, Science Trans Med, 2016), consistent with a microglia response triggered by AD pathology. Importantly, higher biomarker levels of sTREM2 at a given level of beta-amyloid and tau pathology were associated with slower subsequent cognitive decline (Ewers et al. Science Transl Medicine 2019), reduced detrimental effects of ApoE e3 genotype (Franzmeier et al. Mol Neurodeg. 2020) and slower rate of increase in amyloid PET (Ewers et al. EMBO Mol Med. 2020).

Publications

Team

Anna Rubinski, PhD (post-doc)

I obtained a Bachelor’s degree in Biotechnology and Food Engineering and a Master’s degree in Medical Sciences from the Technion – Israel Institute of Technology. After completing my Master’s, I worked in a pharmaceutical company developing next-generation treatments for central nervous system disorders. In 2017 I joined the Ewers Lab for my PhD, where I continue now as post-doc. I’m interested in neuroimaging in Alzheimer’s disease, with a focus on mechanisms of tau spreading and genetics. Outside the lab, I enjoy traveling, hiking, and international cuisine.

Twitter: @AnnaRubinski (https://twitter.com/AnnaRubinski)

Ying Luan, PhD (post-doc)

I obtained my Bachelor degree from Southeast University in China in 2015. Afterwards, I was enrolled in a Master and PhD program in Medical Imaging and Nuclear Medicine at Southeast U, focusing on the hearing loss-related cognitive decline. In September 2019, I joined Michael Ewers’ group as a joint PhD student supported by the Chinese Scholarship Council (CSC)/LMU scholarship. I am currently pursuing post-doctoral work at the Ewers Lab and work as a radiologist. I have a strong interest in the neuroimaging in Alzheimer’s disease, particularly in functional network mapping of tau accumulation and domain-specific cognitive impairment in Alzheimer’s disease. In my spare time, I like travelling and cooking.

Lukai Zheng, PhD student

I grew up in China and studied medicine at West China School of Medicine, Sichuan University (graduated in 2017). After that, I completed my master’s in Neurology at the same university (2020), with a focus on hemorrhagic transformation after ischemic stroke. In October 2020, with a scholarship from the China Scholarship Council, I joined the group of Ewers as a PhD student. My current work focuses on modelling tau pathology progression in Alzheimer’s disease with PET images and brain transcriptome.

Jannis Denecke, PhD student

Following a bachelor’s degree in Psychology, I pursued a master’s degree in Psychology as well as Social and Economic Data Science both at the University of Konstanz. I joined Michael Ewers’ group and the Graduate School of Systemic Neurosciences to follow up with a PhD focusing on brain mechanisms that underlie cognitive resilience in neurodegenerative diseases. Furthermore, I am professionally interested in research methods, network analysis, statistics, and computational modeling. My private interests include photography, cooking, and board games.

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