Objective: The aim of this study was to assess the previous hypothesis about relationship between clinical spectrum of Progressive Supranuclear Palsy (PSP) and tau burden in a series of 37 consecutive autopsied patients with pathological diagnoses of PSP coming from the Navarra Brain Bank.

Background: PSP is the most frequent primary four-repeat tauopathy. Heterogeneous clinical presentations are common in PSP. The pathological basis of these PSP clinical variants is presumed to be the varying anatomical distribution of tau pathology.

Methods: We studied the phenotypic spectrum of PSP by retrospective clinical records review. Classification of clinical variants was made according to predominant clinical features in the first 2 years of the disease. The distribution and severity of tau-related pathology (neuronal tangles, neuropil threads and glial tangles) were assessed (0, absent; 1, sparse; 2, moderate; 3, numerous) using AT8 immunostained sections for all the anatomical regions examined.

Results: The distribution of PSP subtypes was: PSP-Richardson’s syndrome (PSP-RS) 20 (54,1%), PSP-Parkinsonism (PSP-P) 4 (10,8%), PSP-pure akinesia with gait freezing (PSP-PAGF) 1 (2,7%), PSP-non fluent progressive aphasia (PSP-NFPA): 4 (10,8%), PSP-frontotemporal dementia (PSP-FTD) 3 (8,1%), PSP-corticobasal syndrome (PSP-CBS) 1 (2,7%), PSP-cerebellum (PSP-C) 2 (5.4%) and non classifiable (PSP-NC) 2 (5.4%). The overall severity of tau load was no different comparing PSP-RS with atypical subtypes as a whole. The PSP-tau score in PSP-P, as a paradigm of subcortical atypical subtypes, tended to be lower than in RS (p<0,1) similar to previous works. We founded more cortical tau pathology in cortical atypical subtypes (PSP-NFPA, PSP-FTD and PSP-CBS) than PSP-RS (P<0,05) and PSP-P (p<0,05). There were no differences on the subcortical tau burden between PSP subtypes. We founded a negative correlation (ρ=-0,72, p<0,01) between tau burden and survival in the group of atypical subtypes (PSP-P, PSP-PAGF, PSP-NFPA, PSP-FTD, PSP-CBS) although it was not present in the RS phenotype.

Conclusions: PSP complies a broad spectrum of clinical and pathological subtypes. The present study highlights that cortical tau density determines PSP clinical presentation. The disease survival appears to be related to the Tau burden. Further investigation is needed to determine the factors that underlie the anatomical selective vulnerability in PSP and its variants.

References: Respondek G, Stamelou M, Kurz C, Ferguson LW, Rajput A, Chiu WZ, et al. The phenotypic spectrum of progressive supranuclear palsy: a retrospective multicenter study of 100 definite cases. Mov Disord Off J Mov Disord Soc. 2014 Dec;29(14):1758–66. Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord Off J Mov Disord Soc. 2017 Jun;32(6):853–64. Dickson DW, Ahmed Z, Algom AA, Tsuboi Y, Josephs KA. Neuropathology of variants of progressive supranuclear palsy. Curr Opin Neurol. 2010 Aug;23(4):394–400. Williams DR, Holton JL, Strand C, Pittman A, de Silva R, Lees AJ, et al. Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson’s syndrome. Brain J Neurol. 2007 Jun;130(Pt 6):1566–76. Koga S, Parks A, Kasanuki K, Sanchez-Contreras M, Baker MC, Josephs KA, et al. Cognitive impairment in progressive supranuclear palsy is associated with tau burden. Mov Disord Off J Mov Disord Soc. 2017 Oct 30; Yokoyama Y, Toyoshima Y, Shiga A, Tada M, Kitamura H, Hasegawa K, et al. Pathological and Clinical Spectrum of Progressive Supranuclear Palsy: With Special Reference to Astrocytic Tau Pathology. Brain Pathol Zurich Switz. 2016 Mar;26(2):155–66.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-tau-burden-and-distribution-on-the-spectrum-of-psp-subtypes/