Wiersma VI, van Ziel AM, Vazquez-Sanchez S, et al. - Researchers used confocal, automated, super-resolution and electron microscopy to illustrate that the seeding of tau pathology triggers the formation of granulovacuolar degeneration bodies (GVBs, membrane-bound vacuolar structures harboring a dense core that collects in the brains of patients with neurodegenerative disorders, like Alzheimer disease and other tauopathies) in various mouse models in vivo and in primary mouse neurons in vitro. In cultured neurons, but not in astrocytes, seeding-induced intracellular tau aggregation, but not seed exposure alone, led to GVB formation. The extent of tau pathology strongly related to the GVB load. For the established GVB markers CK1δ, CK1ɛ, CHMP2B, pPERK, peIF2α, and pIRE1α, tau-induced GVBs were immunoreactive and had a LAMP1- and LIMP2-positive single membrane that surrounds the dense core and vacuole. In the majority of GVBs, the proteolysis reporter DQ-BSA was discovered, illustrating that GVBs accommodate degraded endocytic cargo. GFP-tagged CK1δ accumulated in the GVB core, whereas GFP-tagged tau or GFP alone did not, symbolizing selective targeting of cytosolic proteins to GVBs. Thus, the first in vitro model for GVB formation by seeding tau pathology in primary neurons was established in this study. In the human brain, the tau-induced GVBs have the marker signature and morphological features of GVBs. Moreover, it was exhibited that GVBs are lysosomal structures characterized by the accumulation of a particular subset of proteins in a dense core.