We are pleased to announce the publication of our latest research article in Nature Scientific Reports:
👉 “Functional discrimination of CSF from Alzheimer’s patients in a brain-on-chip platform” .
This work highlights the potential of organ-on-chip technologies to provide functional and translational insights into patient-derived samples, offering a promising path toward improved diagnostics and patient stratification in neurodegenerative diseases.
Alzheimer’s disease: a pressing global challenge
Alzheimer’s disease (AD) is the leading cause of dementia worldwide and affects millions of patients each year. Despite decades of research, diagnosing AD remains complex and often relies on invasive, time-consuming, and costly methods such as brain imaging, neuropsychological testing, or cerebrospinal fluid (CSF) biomarker analysis.
Currently, AD is the only neurodegenerative disease for which specific biomarkers (such as amyloid beta peptide Aβ) are clinically available. However, no such tools exist for most other neurodegenerative conditions. This diagnostic gap delays accurate patient care and limits access to clinical trials and novel therapies.
There is therefore an urgent need for innovative technologies capable of bridging this gap and enabling faster, more reliable, and less invasive diagnostics.
NETRI’s Brain-on-Chip approach
At NETRI, we have developed a compartmentalized microfluidic Brain-on-Chip platform that integrates human induced pluripotent stem cell (iPSC)-derived neurons and microelectrode array (MEA) technology.
This platform allows researchers to:
Recreate complex human neuronal networks in vitro.
Expose these networks to biological fluids such as CSF.
Record neuronal responses in real time using electrophysiological metrics.
In this study, glutamatergic neurons were exposed to either synthetic amyloid beta oligomers or to CSF samples from confirmed Alzheimer’s patients and non-neurodegenerative individuals. By measuring key electrophysiological parameters, we demonstrated that our Brain-on-Chip system can tend to distinguish Alzheimer’s CSF from non-neurodegenerative CSF, validating the concept of neurons acting as biosensors for disease-specific signatures
Key results
Neurons on chip matured and exhibited spontaneous activity, proving the robustness of the platform.
Exposure to amyloid beta oligomers led to measurable decreases in neuronal activity and network synchrony.
When exposed to CSF samples from patients, the platform revealed differential effects between Alzheimer’s and non-neurodegenerative fluids, showing trends that support functional discrimination.
The system offers a non-invasive and functional approach to study CSF effects and explore new biomarkers beyond classical biochemical assays.
While these results represent an early proof-of-concept, they highlight the potential of Brain-on-Chip technologies to expand diagnostic capabilities for Alzheimer’s and other neurodegenerative diseases.
A collaborative achievement
This publication is the result of an outstanding collaboration between:
NETRI (Lyon, France)
Hospices Civils de Lyon – Department of Biochemistry and Molecular Biology, Neurodegenerative Pathologies (Bron, France)
Lyon Neurosciences Research Center (CNRS UMR 5292 / INSERM U1028)
ETAP-Lab – Preclinical Efficacy CRO (Vandoeuvre-Lès-Nancy, France)
Authors:
Louise Miny, Jessica Rontard, Ahmad Allouche, Nicolas Violle, Louise Dubuisson, Aurélie Batut, Alexandre Ponomarenko, Rania Talbi, Hélène Gautier, Benoît G. C. Maisonneuve, Serge Roux, Florian Larramendy, Thibault Honegger & Isabelle Quadrio.
We warmly thank the Hospices Civils de Lyon for their trust and support in providing access to clinical samples and expertise.
Looking ahead
This proof-of-concept study paves the way for further developments:
Increasing the number of patient samples to strengthen statistical power.
Refining electrophysiological analyses with additional biomarkers and computational tools.
Expanding the platform to other neurodegenerative diseases beyond Alzheimer’s.
Contributing to personalized medicine by enabling patient-specific functional diagnostics.
At NETRI, we believe that Organs-on-Chip technologies are not just laboratory tools—they are enablers of a new era in biomedical research, accelerating therapeutic innovation and improving patient care.