Objective: To determine the most accurate and reliable tau PET tracers for providing differential diagnosis of PSP and CBD from PD.

Background: Parkinsonism is classified as the combination of bradykinesia with postural instability, tremor, or rigidity. The most common parkinsonism is PD, affecting 1% of individuals over the age of 60. PSP and CBD are atypical parkinsonisms that are classified as tauopathies; they may present with similar early clinical manifestations to PD, but their neuropathology differs. For this reason, it is important to develop biomarkers to aid in early differential diagnosis. One of the most promising avenues of biomarker development has been PET neuroimaging of protein hallmarks of these disease, including alpha-synuclein, and, of particular interest to this study—tau. The protein aggregates underlying PSP and CBD pathology are caused by hyper-phosphorylation of the tau protein. Over the past decade, there has been an attempt to determine the most reliable PET tracer for imaging tau bundles in atypical parkinsonisms.

Method: We conducted an English language electronic database search using Pubmed and Web of Science from 1999 – 2022. Records were screened for duplicates and review papers. The studies included are case-control studies for PSP, CBD, and PD that report tracer binding in at least one ROI as mean ± SD. Using Meta-Essentials (1.0), we conducted a random-effects model to assess standardized mean differences between subject groups for each tau PET tracer. Furthermore, we used meta-regressions to assess associations between effect sizes and potential confounds like age, publication year, and disease duration.

Results: The studies included present significant heterogeneity, up to I² > 90%. The most widely studied tau PET tracer, flortaucipir, provides distinguishing ability for PSP in the pallidum, dentate nucleus, and temporal lobe (p < 0.05). Furthermore, there is a trend towards higher tracer binding in PSP patients in the putamen, frontal, and parietal lobes, although these differences are not significant.

Conclusion: Overall, the available tau PET tracers provide distinguishing capacity in a few of the ROIs set out for this study, specifically in the basal ganglia and dentate nucleus. Given the limited sample sizes and heterogeneity of the results presented here, future work is needed to provide a more accurate picture of biomarker development progress for these atypical parkinsonisms.

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