Pathological, clinical and genetic heterogeneity in progressive supranuclear palsy

We have identified two groups of patients with clinically typical and atypical, pathologically diagnosed progressive supranuclear palsy (PSP), and investigated their genetic and molecular pathological characteristics. Those with clinically typical PSP are more likely to have the PSP susceptibility genotype and to have the deposition of PSP‐type hyperphosphorylated tau protein. The clinically atypical PSP group contains a number of different clinical syndromes, including an l‐dopa unresponsive bradykinetic syndrome and a clinical syndrome closely resembling idiopathic Parkinson’s disease. The clinically atypical PSP group are less likely to have the PSP susceptibility genotype and often have the deposition of Alzheimer’s disease paired helical filament type hyperphosphorylated tau. This study suggests that the tau PSP susceptibility genotype is most strongly associated with clinically typical PSP. Neurofibrillary tangle parkinsonian disorders, which pathologically resemble PSP but involve the deposition of Alzheimer’s disease‐type tau often without involvement of the tau susceptibility genotype, need to be distinguished for diagnostic and research purposes.