Label-free Aβ plaque detection in Alzheimer's disease brain tissue using infrared microscopy and neural networks
Dajana Müller, Dominik Röhr, Baayla D.C. Boon, Maximilian Wulf, Thomas Arto, Jeroen J.M. Hoozemans, Katrin Marcus, Annemieke J.M. Rozemüller, Frederik Großerueschkamp, Axel Mosig, Klaus Bernhard Gerwert · Heliyon · 2025
We present a novel method for the label-free detection of amyloid-beta (Aβ) plaques, the key hallmark of Alzheimer's disease, in human brain tissue sections. Conventionally, immunohistochemistry (IHC) is employed for the characterization of Aβ plaques, hindering subsequent analysis. Here, a semi-supervised convolutional neural network (CNN) is trained to detect Aβ plaques in quantum cascade laser infrared (QCL-IR) microscopy images. Laser microdissection (LMD) is then used to precisely extract plaques from snap-frozen, unstained tissue sections. Mass spectrometry-based proteomics reveals a loss of soluble proteins in IHC stained samples. Our method prevents this loss and provides a novel tool that expands the scope of molecular analysis methods to chemically native plaques. Insight into soluble plaque components will complement our understanding of plaques and their role in Alzheimer's disease.