Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy

Background Elevated CSF tau is considered a biomarker of neuronal injury in newly developed Alzheimer's disease (AD) and mild cognitive impairment (MCI) criteria. However, previous studies have failed to detect alterations of tau species in other primary tauopathies. We assessed CSF tau protein abnormalities in AD, a tauopathy with prominent A beta pathology, and progressive supranuclear palsy (PSP), a primary tauopathy characterised by deposition of four microtubule-binding repeat (4R) tau with minimal A beta pathology. Methods 26 normal control (NC), 37 AD, and 24 patients with PSP participated in the study. AD and PSP were matched for severity using the clinical dementia rating sum of boxes (CDR-sb) scores. The INNO BIA AlzBio3 multiplex immunoassay was used to measure CSF A beta, total t, and ptau181. Additional, novel ELISAs targeting different N-terminal and central tau epitopes were developed to examine CSF tau components and to investigate interactions between diagnostic group, demographics and genetic variables. Results PSP had lower CSF N-terminal and C-terminal t concentrations than NC and AD measured with the novel tau ELISAs and the standard AlzBio3 tau and ptau assays. AD had higher total tau and ptau levels than NC and PSP. There was a gender by diagnosis interaction in AD and PSP for most tau species, with lower concentrations for male compared to female patients. Conclusions CSF tau fragment concentrations are different in PSP compared with AD despite the presence of severe tau pathology and neuronal injury in both disorders. CSF tau concentration likely reflects multiple factors in addition to the degree of neuronal injury.