Tauopathies represent a large class of neurological and movement disorders 
characterized by abnormal intracellular deposits of the microtubule-associated 
protein tau. It is now well established that mis-splicing of tau exon 10, 
causing an imbalance between three-repeat (3R) and four-repeat (4R) tau 
isoforms, can cause disease; however, the underlying mechanisms affecting tau 
splicing in neurons remain poorly understood. The small noncoding microRNAs 
(miRNAs), known for their critical role in posttranscriptional gene expression 
regulation, are increasingly acknowledged as important regulators of alternative 
splicing. Here, we identified a number of brain miRNAs, including miR-124, 
miR-9, miR-132 and miR-137, which regulate 4R:3R-tau ratios in neuronal cells. 
Analysis of miRNA expression profiles from sporadic progressive supranuclear 
palsy (PSP) patients, a major 4R-tau tauopathy, showed that miR-132 is 
specifically down-regulated in disease. We demonstrate that miR-132 directly 
targets the neuronal splicing factor polypyrimidine tract-binding protein 2 
(PTBP2), which protein levels were increased in PSP patients. miR-132 
overexpression or PTBP2 knockdown similarly affected endogenous 4R:3R-tau ratios 
in neuronal cells. Finally, we provide evidence that miR-132 is inversely 
correlated with PTBP2 during post-natal brain development at the time when 
4R-tau becomes expressed. Taken together, these results suggest that changes in 
the miR-132/PTBP2 pathway could contribute to the abnormal splicing of tau exon 
10 in the brain, and sheds light into the potential role played by miRNAs in a 
subset of tauopathies.