In the present study, we applied the iDISCO+ volume immunostaining and clearing technology, in combination with LSFM, to explore the cytoarchitecture, tau cytoskeletal pathology and their potential relationships in the human LC/PC region of postmortem brains from subjects afflicted by various stages of the Alzheimer’s disease spectrum. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.