CLARITY in Alzheimer’s Research: Merging Tissue Transparency with Next-Gen Neurotechnologies

CLARITY is a technique that makes tissues optically transparent, enabling the clear visualization of complex cellular and subcellular structures with relative ease. Traditionally, this technique has been used to visualize the pathologies of certain diseases. In the case of Alzheimer’s disease (AD), the CLARITY technique of clearing lipids from tissues has enabled precise visualization of amyloid-beta (Aβ) and tau pathologies with a temporal analysis of the extent of protein aggregation associated with disease progression. This information has been invaluable for determining the progression of AD. Moreover, the structural characteristics of Aβ plaques and neurofibrillary tangles provide details about aggregation patterns. Here, we highlight critical insights into the potential applications of the CLARITY technique in conjunction with other modalities. We elucidated microscopy techniques, namely confocal microscopy and light-sheet microscopy, which are often used to detect fluorescently labeled compounds within cells, aiding in the qualitative and quantitative estimation of target proteins. Additionally, we discuss the application of super-resolution expansion microscopy (SREM) to increase the resolution of tissue images without compromising molecular specificity. We also expounded on the application of CLARITY-based imaging in improving optogenetics and organoid development. Furthermore, we highlight the potential of CLARITY in assisting the formulation and validation of machine learning algorithms and conducting hypothesis testing.