Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy. Issue 3 (4th June 2014)

• Record Type: Journal Article
• Authors: Wagshal, Dana; Sankaranarayanan, Sethu; Guss, Valerie; Hall, Tracey; Berisha, Flora; Lobach, Iryna; Karydas, Anna; Voltarelli, Lisa; Scherling, Carole; Heuer, Hilary; Tartaglia, Maria Carmela; Miller, Zachary; Coppola, Giovanni; Ahlijanian, Michael; Soares, Holly; Kramer, Joel H; Rabinovici, Gil D; Rosen, Howard J; Miller, Bruce L; Meredith, Jere; Boxer, Adam L
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 86:Issue 3(2015)
• Page Start: 244
• Page End: 250
• Publication Date: 2014-06-04
• Subjects: Alzheimer's Disease -- CSF; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2014-308004
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : 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.