RT Journal Article
SR Electronic
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
FD BMJ Publishing Group Ltd
SP 244
OP 250
DO 10.1136/jnnp-2014-308004
VO 86
IS 3
A1 Dana Wagshal
A1 Sethu Sankaranarayanan
A1 Valerie Guss
A1 Tracey Hall
A1 Flora Berisha
A1 Iryna Lobach
A1 Anna Karydas
A1 Lisa Voltarelli
A1 Carole Scherling
A1 Hilary Heuer
A1 Maria Carmela Tartaglia
A1 Zachary Miller
A1 Giovanni Coppola
A1 Michael Ahlijanian
A1 Holly Soares
A1 Joel H Kramer
A1 Gil D Rabinovici
A1 Howard J Rosen
A1 Bruce L Miller
A1 Jere Meredith
A1 Adam L Boxer
YR 2015
UL http://jnnp.bmj.com/content/86/3/244.abstract
AB 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.