Rapid Biomarker Screening of Alzheimer's Disease by Interpretable Machine Learning and Graphene-Assisted Raman Spectroscopy.

The study of Alzheimer's disease (AD), the most common cause of dementia, faces challenges in terms of understanding the cause, monitoring the pathogenesis, and developing early diagnoses and effective treatments. Rapid and accurate identification of AD biomarkers in the brain is critical to providing key insights into AD and facilitating the development of early diagnosis methods. In this work, we developed a platform that enables a rapid screening of AD biomarkers by employing graphene-assisted Raman spectroscopy and machine learning interpretation in AD transgenic animal brains. Specifically, we collected Raman spectra on slices of mouse brains with and without AD and used machine learning to classify AD and non-AD spectra. By contacting monolayer graphene with the brain slices, the accuracy was increased from 77% to 98% in machine learning classification. Further, using a linear support vector machine (SVM), we identified a spectral feature importance map that reveals the importance of each Raman wavenumber in classifying AD and non-AD spectra. Based on this spectral feature importance map, we identified AD biomarkers including Aβ and tau proteins and other potential biomarkers, such as triolein, phosphatidylcholine, and actin, which have been confirmed by other biochemical studies. Our Raman-machine learning integrated method with interpretability will facilitate the study of AD and can be extended to other tissues and biofluids and for various other diseases.