Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Abstract

Progressive supranuclear palsy (PSP), once simply considered a common cause of atypical parkinsonism is now recognized as a spectrum of motor and behavioral syndromes associated with a specific four repeat (4R) tau neuropathology at autopsy. There are currently no effective treatments for PSP, but because PSP is strongly linked biochemically and genetically to tau protein abnormalities, there is a growing interest in pursuing clinical trials of new tau-directed therapies for this disorder. Such new tau therapies are envisioned to have disease-modifying effects by reducing brain levels of toxic forms of tau or compensating for loss of tau function. To be most effective, these treatments will need to be initiated at early stages of disease. New research criteria that recognize early forms of PSP and operationalize diagnosis of the full spectrum of clinical phenotypes have recently been published. These criteria and new clinical trial designs have benefited from rapid advances in MRI, physiological and fluid biomarker development for PSP. As tau pathology is also central to Alzheimer’s disease and chronic traumatic encephalopathy, it is believed that a successful tau therapeutic for PSP would inform the treatment of other neurodegenerative diseases.

Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI study

“…Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease associated with 4R tauopathy 1. The most common clinical presentation of PSP is Richardson’s syndrome (PSP-RS), in which patients have insidious early onset of a symmetric akinetic-rigid syndrome with vertical supranuclear gaze palsy, early backward falls and frontal dysfunction 1 2.…”

Pearls & Oy-sters: Ocular motor apraxia as essential differential diagnosis to supranuclear gaze palsy

“…1,2 This case demonstrates the relevance of considering OA as clinical clue for the diagnosis of CBS. OA points to a dysfunction in the area of the frontal eye fields (voluntary saccade initiation).…”

“…1,2 He was unable to elicit voluntary pursuit movements and saccades in all directions in a stationary head position, while this deficit could be overcome by activation of the vestibuloocular reflex during passive head movements. This finding would indeed qualify for SGP according to the standard definition of the term.…”

Tau Diagnostics and Clinical Studies

“…html), we are now ideally positioned to discuss advances and future projections for tau diagnostics and clinical trials. This short review presents our own perspectives, trying to portray an objective view (Gozes 2002;Matsuoka et al 2007;VulihShultzman et al 2007;Matsuoka et al 2008;Shiryaev et al 2009;Gozes 2010aGozes , 2010bKnake et al 2010;Shiryaev et al 2010;Stamelou et al 2010;Gozes 2011;Hoglinger et al 2011;Idan-Feldman et al 2012;Jouroukhin et al 2012;Jouroukhin et al 2013;Boxer et al 2014;Gozes et al 2014;Hoglinger et al 2014;Magen et al 2014;Schirer et al 2014;Tolosa et al 2014;Kouri et al 2015, Sun et al 2015, Levin et al 2016, Stamelou and Hoglinger 2016Boxer et al 2017;Gozes 2017;Hansson et al 2017;Hoglinger et al 2017;Hoglund et al 2017;Respondek et al 2017). …”