Correlation of tau pathology in eye movement related brainstem nuclei in cases of progressive supranuclear palsy (PSP) and a proposed role of perineuronal nets

Publication date: March 2016
Source:Clinical Neurophysiology, Volume 127, Issue 3
Author(s): A. Horn, A. Fröschl, J. Feige, S. Röber, H. Kretzschmar
BackgroundProgressive supranuclear palsy (PSP) is characterized by hyperphosphorylated tau protein (HTP) accumulations in different brain regions. A hallmark of clinical symptoms is a vertical gaze palsy, which may be accompanied by horizontal gaze palsy, whereas the VOR is rather preserved until late in the disease. Based on monkey studies functional cell groups of the oculomotor system including transmitters have been identified in the human brainstem (Büttner-Ennever & Horn, 2010).MethodsTo study the spread of the disease through the oculomotor premotor network sections of 8 archival PSP cases with different eye movement deficits were immunostained for HTP. The analysis involved the glutaminergic rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF) and paramedian pontine reticular formation (PPRF), the glycinergic saccadic omnipause neurons (OPN), the cholinergic oculomotor nucleus (nIII) and the vestibular nuclei (VN). Since the RIMLF and nIII contain well-developed perineuronal nets (PN) (Horn et al., 2003), we further stained sections of the PSP cases for the presence of aggrecan (ACAN) and HTP to prove a possible protective role of PNs as suggested from Alzheimer's disease cases (Morawski et al., 2010).ResultsAll PSP-cases showed HTP-staining in neurons and glia of RIMLF, PPRF and OPNs, in late cases in motonuclei as well. Thereby a correlation between eye movement deficits and degeneration of premotor gaze centers and the complete pathways to motoneurons was found, whereas the VN are less affected. The analysis of PNs revealed that ACAN-based PNs were mainly found around HTP-negative neurons, and only few HTP-positive neurons showed weak ACAN staining.ConclusionsThe early and more severe degeneration of premotor centers compared to nIII support a hypothesis that in PSP the pathology progresses along neuronal chains in an anterograde fashion, and it is not confined to specific transmitters. The severe tau pathology in RIMLF and nIII in late PSP cases implies that the presence of PNs may not protect them from degeneration, but on a cellular basis the integrity of PNs is affected by tau-pathology.Support: BMBF (IFB-01EO0901, Brain-Net-01GI0505).



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