• Dana Wagshal, Sethu Sankaranarayanan, Valerie Guss, Tracey Hall, Flora Berisha, Iryna Lobach, Anna Karydas, Lisa Voltarelli, Carole Scherling, Hilary Heuer, Maria Carmela Tartaglia, Zachary Miller, Giovanni Coppola, Michael Ahlijanian, Holly Soares, Joel H Kramer, Gil D Rabinovici, Howard J Rosen, Bruce L Miller, Jere Meredith, and Adam L Boxer.
• Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA.
• J. Neurol. Neurosurg. Psychiatr.. 2015 Mar 1;86(3):244-50.

BackgroundElevated 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.Methods26 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.ResultsPSP 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.ConclusionsCSF 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.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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