Combining cerebrospinal fluid and PI‐2620 tau‐PET for biomarker‐based stratification of Alzheimer's disease and 4R‐tauopathies

Abstract

Abstract INTRODUCTION Recent advances in biomarker research have improved the diagnosis and monitoring of Alzheimer's disease (AD), but in vivo biomarker‐based workflows to assess 4R‐tauopathy (4RT) patients are currently missing. We suggest a novel biomarker‐based algorithm to characterize AD and 4RTs. METHODS We cross‐sectionally assessed combinations of cerebrospinal fluid measures (CSF p‐tau 181 and t‐tau) and 18 F‐PI‐2620 tau‐positron emission tomography (PET) in patients with AD ( n = 64), clinically suspected 4RTs (progressive supranuclear palsy or corticobasal syndrome, n = 82) and healthy controls ( n = 19). RESULTS Elevated CSF p‐tau 181 and cortical 18 F‐PI‐2620 binding was characteristic for AD while normal CSF p‐tau 181 with elevated subcortical 18 F‐PI‐2620 binding was characteristic for 4RTs. 18 F‐PI‐2620‐assessed posterior cortical hypoperfusion could be used as an additional neuronal injury biomarker in AD. DISCUSSION The specific combination of CSF markers and 18 F‐PI‐2620 tau‐PET in disease‐specific regions facilitates the biomarker‐guided stratification of AD and 4RTs. This has implications for biomarker‐aided diagnostic workflows and the advancement in clinical trials. Highlights Novel biomarker‐based algorithm for differentiating AD and 4R‐tauopathies. A combination of CSF p‐tau 181 and 18 F‐PI‐2620 discriminates AD versus 4R tauopathies. Hypoperfusion serves as an additional neuronal injury biomarker in AD.