TFEB Overexpression in the P301S Model of Tauopathy Mitigates Increased PHF1 Levels and Lipofuscin Puncta and Rescues Memory Deficits

Abstract Transcription factor EB ( TFEB) was recently shown to be a master regulator of autophagylysosome pathway. Here, we successfully generated and characterized transgenic mice overexpressing flag- TFEB. Enhanced autophagyin the flag- TFEBtransgenic mice was confirmed by an increase in the cellular autophagymarkers, as determined by both immunoblots and transmission electron microscopy. Surprisingly, in the flag- TFEBmice we observed increased activity of senescence-associated β-galactosidase by ∼66% of neurons in the cortex ( p p p p p p p p p pin vivo , reduce levels of PHF-tau, and thereby reverse the deposition of lipofuscingranules and memory deficits.