The prioritization of biomarkers in the diagnostic workup of motor tauopathy

Abstract

AbstractMotor tauopathies represent a spectrum of degenerative, poorly levodopa‐responsive parkinsonisms unified by the pathological accumulation of hyperphosphorylated tau protein fragments in the brain. The principal entities, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are rare conditions (<10 per 100,000) and present with non‐amnestic cognitive impairment ‐ mostly involving frontal‐subcortical networks – in around 40% of patients at baseline. Additionally, the phenotypic PSP spectrum expresses with oculomotor dysfunction, falls and bulbar symptoms at varying degrees. On the other hand, CBD tauopathy is the most frequent aetiology underlying the corticobasal syndrome (CBS) that is a multifaceted disorder characterized by a markedly asymmetric Parkinsonism with apraxia and neocortical deficits. Paralleling the clinical symptoms, the distribution of functional and metabolic impairment specifically involves different brain regions in PSP and CBD. Hence, metabolism assessment by FDG‐positron emission tomography (PET) allows for accurate distinction of motor tauopathies from other parkinsonisms or one with another (AUC 0.80 and 0.92‐0.97, respectively). In this context, the European Intersociety Consensus Diagnostic Task Force recommends the use of FDG‐PET as the first‐level diagnostic biomarker to achieve early and accurate differential diagnosis of motor tauopathies. Afterwards, the assessment of CSF biomarkers of Alzheimer’s disease (AD) is advised to identify that minority of cases of CBS underpinned by an AD aetiology (10‐20%). With this sequence of biomarkers, the diagnostic workflow aims to an early identification of motor tauopathies and advocates in‐depth etiological investigation of CBS where access to AD‐specific drugs, when available, should be considered in a non‐negligible proportion of patients.