Abstract: BANF1, PPP2CA, and ANKLE2 were identified as genes that promote tau aggregation when disrupted. Improved tauopathy models such as cells, tissues, or animals having mutations in or inhibition of expression of BANF1 and/or PPP2CA and/or ANKLE2 are provided. Methods of using such improved tauopathy models for assessing therapeutic candidates for the treatment of a tauopathy, methods of making the improved tauopathy models, and methods of accelerating or exacerbating tau aggregation in a tauopathy model are also provided.

Abstract: BANF1, PPP2CA, and ANKLE2 were identified as genes that promote tau aggregation when disrupted. Improved tauopathy models such as cells, tissues, or animals having mutations in or inhibition of expression of BANF1 and/or PPP2CA and/or ANKLE2 are provided. Methods of using such improved tauopathy models for assessing therapeutic candidates for the treatment of a tauopathy, methods of making the improved tauopathy models, and methods of accelerating or exacerbating tau aggregation in a tauopathy model are also provided.

Abstract: Provided herein are methods of inhibiting tau aggregation in a cell or a subject, comprising administering a LEM domain-containing protein 2 (LEMD2), a charged multivesicular body protein 7 (CHMP7), or an inner nuclear membrane protein Man 1 (LEMD3) or a nucleic acid encoding the LEMD2, the CHMP7, or the LEMD3 to the cell or the subject. Also provided herein are methods of treating or preventing a tauopathy in a subject, comprising administering LEMD2, CHMP7, or LEMD3 or a nucleic acid encoding the LEMD2, the CHMP7, or the LEMD3 to the subject, wherein the LEMD2, the CHMP7, or the LEMD3 inhibits tau aggregation in a cell in the subject. Also provided are nucleic acids encoding LEMD2, CHMP7, or LEMD3 (e.g., in an expression construct and operably linked to a heterologous promoter).