Mouse and Human Tau Expression in Different Brain Areas

J Alzheimers Dis Rep. 2022 Nov 3;6(1):677-684. doi: 10.3233/ADR-220051. eCollection 2022.

Abstract

Background: An increase in tau protein is believed to be necessary for tau aggregation. However, whether this is due to increased expression of the endogenous tau promoter or protein accumulation due to proteostasis failure remains uncertain.

Objective: To analyze the expression of GFP protein under endogenous tau promoter across different ages and within different brain areas.

Methods: We have measured direct expression of Mapt gene promotor by western blot and immunofluorescence, by means of a commercial tau knock-out mice generated by integrating GFP-encoding cDNA into exon 1 of the Mapt gene. Besides, we have analyzed the MAPT gene expression in human samples.

Results: Mapt expression is similar in the cortex, hippocampus, and cerebellum in mice and in human samples although some differences exist between dentate gyrus and CA1 hippocampal areas in mice. Besides, we have analyzed the murine Mapt gene expression during aging (at 2, 6, 12, and 18 moths) and no differences in endogenous tau promoter expression were observed.

Conclusion: Our results suggest that Mapt promoter activity is similar in the brain areas studied and, therefore, tau accumulation due to aging is likely due to proteostasis failure rather than occurring at the transcriptional level.

Keywords: Aging; neurodegeneration; promotor expression; tau.