TY - JOUR T1 - Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 244 LP - 250 DO - 10.1136/jnnp-2014-308004 VL - 86 IS - 3 AU - Dana Wagshal AU - Sethu Sankaranarayanan AU - Valerie Guss AU - Tracey Hall AU - Flora Berisha AU - Iryna Lobach AU - Anna Karydas AU - Lisa Voltarelli AU - Carole Scherling AU - Hilary Heuer AU - Maria Carmela Tartaglia AU - Zachary Miller AU - Giovanni Coppola AU - Michael Ahlijanian AU - Holly Soares AU - Joel H Kramer AU - Gil D Rabinovici AU - Howard J Rosen AU - Bruce L Miller AU - Jere Meredith AU - Adam L Boxer Y1 - 2015/03/01 UR - http://jnnp.bmj.com/content/86/3/244.abstract N2 - Background Elevated CSF τ 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 τ species in other primary tauopathies. We assessed CSF τ protein abnormalities in AD, a tauopathy with prominent Aβ pathology, and progressive supranuclear palsy (PSP), a primary tauopathy characterised by deposition of four microtubule-binding repeat (4R) τ with minimal Aβ 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 Aβ, total τ, and ptau181. Additional, novel ELISAs targeting different N-terminal and central τ epitopes were developed to examine CSF τ components and to investigate interactions between diagnostic group, demographics and genetic variables. Results PSP had lower CSF N-terminal and C-terminal τ concentrations than NC and AD measured with the novel τ ELISAs and the standard AlzBio3 τ and ptau assays. AD had higher total τ and ptau levels than NC and PSP. There was a gender by diagnosis interaction in AD and PSP for most τ species, with lower concentrations for male compared to female patients. Conclusions CSF τ fragment concentrations are different in PSP compared with AD despite the presence of severe τ pathology and neuronal injury in both disorders. CSF τ concentration likely reflects multiple factors in addition to the degree of neuronal injury. ER -