Cerebrospinal Fluid Neuroinflammatory Signature in Alzheimer´s Disease and Related Proteopathies

2022, 2023


Neuroinflammation is a crucial process during the pathogenesis of Alzheimer’s disease (AD) and is largely delineated by the activation of glial cells in the brain. During the inflammatory response, microglia, astrocytes and oligodendrocytes undergo different activation stages manifested by specific alterations in their genetic information. The so-called transcriptome changes are eventually reflected by the upregulation or downregulation of protein expressions in the brain and molecular alterations in the surrounding cerebrospinal fluid (CSF). Although it is now possible to measure protein changes in CSF using state-of-the-art technologies, it is virtually impossible in humans to determine which cellular processes in the brain underlie these changes of protein concentrations in the CSF. We have established a neuroinflammatory antibody panel for multiplexed imaging, allowing us to label more than 50 protein markers simultaneously within the same tissue section. We also have established that the vast majority of these proteins are detectable in humans, and many of them change in patients with AD. This research initiative will help to better understand CSF protein changes in AD patients and link them to neuroinflammatory responses in the human brain.


It is now well-accepted that neuroinflammation contributes significantly to the pathogenesis of Alzheimer´s disease (AD) and related cerebral proteopathies. However, little is known about how brain inflammatory states are reflected by molecular biomarker changes in bodily fluids. We have identified a panel of 25 proteins in cerebrospinal fluid (CSF) that may capture the neuroinflammatory states in AD patients. In this project, we aim to validate this protein panel and test the panel in well-characterized AD patient cohorts. The ultimate goal is to develop a multiplex immunoassay for these CSF proteins to assess human neuroinflammatory brain states in AD and related proteopathies.

Funding to Date



Biomarkers/Diagnostics/Studies of Risk & Resilience, Foundational


Mathias Jucker, Ph.D.

Stefan Lichtenthaler, Ph.D.

Stephan Kaeser, Ph.D.

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