Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Novel Therapeutic Targets and Biomarkers for the Treatment of Progressive Supranuclear Palsy

Version 1 : Received: 10 June 2020 / Approved: 12 June 2020 / Online: 12 June 2020 (09:41:06 CEST)

How to cite: Tyer, I.; Hill, A. Novel Therapeutic Targets and Biomarkers for the Treatment of Progressive Supranuclear Palsy. Preprints 2020, 2020060147 (doi: 10.20944/preprints202006.0147.v1). Tyer, I.; Hill, A. Novel Therapeutic Targets and Biomarkers for the Treatment of Progressive Supranuclear Palsy. Preprints 2020, 2020060147 (doi: 10.20944/preprints202006.0147.v1).

Abstract

Progressive supranuclear palsy (PSP) is a sporadic parkinsonism tauopathy characterised by the deposition of aggregations of abnormal, hyperphosphorylated four-repeat tau (4R-tau). A revised clinical diagnostic criterion for PSP allows early presentations for the full spectrum of clinical phenotypes to be recognised enabling doctors to make a more accurate diagnosis. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule-associated protein tau (MAPT). Research into the biochemical and pathological pathways of tau is vital to improve the chances of developing an effective diagnostic biomarker to monitor tau pathogenesis. Neuroimaging biomarkers, such as tau PET ligands, are proving the most successful tool in providing a differential diagnosis between neurodegenerative disorders. There are currently no effective treatments for PSP, however tau-directed therapies in the last five years have rapidly advanced. Latest tau therapies are proposed to have disease-modifying effects by reducing toxic aggregations of tau through manipulating tau gene expression. After encouraging results from long awaited trials, additional funding is being injected into this field and with new results expected, this proves an exciting area for scientific discovery. This paper reviews advances in pathophysiology, diagnosis, biomarkers and disease-modifying therapeutic treatments for PSP.

Subject Areas

PSP; Progressive Supranuclear Palsy; 4R-tau; four-repeat tau; MAPT; Microtubule-associated ligand; PET; Positron Emission Tomography

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