In several neurodegenerative diseases, commonly referred to as tauopathies, pathological forms of the microtubule-associated protein tau spread in a prion-like manner from donor cells to surrounding (recipient) cells, which clinically correlates with the progressive decline in cognition and cell death. Low density lipoprotein receptor-related protein 1 (LRP1) regulates the endocytosis of tau in neurons and thus its subsequent spread. This LRP1-mediated endocytosis is depended upon regulation of actin. The major regulator of actin filament dynamics is tropomyosin, a family of proteins, shown to be associated with endocytosis. Previously we have reported abundant post-synaptic expression of tropomyosins in central nervous system neurons. Therefore, dissecting the role of tropomyosins in tau-propagation is important to better understand tau spread in the disease. To determine the effect of tropomyosin deletion in tau propagation, 3 months old male and female tropomyosin knockout and C57BL6 wild type (WT) control mice were stereotaxically injected with the pathogenic form of human tau [packaged into adeno-associated virus (AAVs)] into the right hippocampus. After 7 weeks of injection all mice were euthanized, perfused, fixed and their brains were collected. Further, the whole brains were processed and sectioned for immunohistochemistry to track the spreading of tau among the different groups. The results indicate that there is an alteration of tau levels in tau recipient neurons in the tropomyosin knockout mice compared to recipient neurons in WT control mice. This indicates that regulation of tau uptake by tropomyosins in recipient neurons is critical for mediating tau spread in the disease.