JOURNAL ARTICLE

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

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, Adam L Boxer
Journal of Neurology, Neurosurgery, and Psychiatry 2015, 86 (3): 244-50
24899730

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.

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