title: A combination of CSF tau ratio and midsaggital midbrain-to-pons atrophy for the early diagnosis of progressive supranuclear palsy.
abstract: Cerebrospinal fluid (CSF) tau ratio decrease (33kDa/55kDa forms) and mid-saggital midbrain-to-pons (MP) atrophy have been suggested as diagnostic markers for progressive supranuclear palsy (PSP). The usefulness of their combined evaluation has never been tested. We evaluated the CSF tau ratio and the MP atrophy as a combined marker for early identification of PSP. A total of 87 subjects, namely 18 PSP, 25 controls (CON), 16 corticobasal syndrome (CBS), and 28 frontotemporal dementia (FTD), were included. Each subject underwent a lumbar puncture and a conventional MRI scan to assess CSF tau 33 kDa/55 kDa ratio and mid-saggital MP measure, respectively. CSF tau ratio and MP ratio were significantly reduced in PSP patients when compared to CON, CBS, and FTD (p< 0.001). Data-based "optimal" combination of CSF tau ratio and MP measure was defined, and the combined marker TrMp= sqrt[3]{CSF Tau ratio}} × {MP ratio} was considered. Considering the combined marker, the difference between the area under the curve (dAUC) of the receiver operating characteristic analysis in PSP versus the various subgroups was higher by about 10% than that obtained by each marker individually. In PSP versus others, a proposed "best" cut-off of TrMP = 0.182 resulted in 94.2% sensitivity and 84.0% specificity. When patients with onset of symptoms ≤ 2 years were included, TrMP resulted significantly decreased in PSP compared to CBS (p< 0.001) and FTD (p< 0.001). The combined marker increases the discriminative power in identifying PSP and suggests that the interplay of different markers should be considered in future trials to enhance diagnostic accuracy from the early stages.
authors.affiliation: The Centre for Aging Brain and Dementia, Department of Neurology, University of Brescia, Brescia, Italy. bborroni@inwind.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Matteo
authors.initials: M
authors.lastname: Malinverno
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.forename: Lucilla
authors.initials: L
authors.lastname: Parnetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Agosti
authors.forename: Antonella
authors.initials: A
authors.lastname: Alberici
authors.forename: Enrico
authors.initials: E
authors.lastname: Premi
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bonuccelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Gasparotti
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000368:Aged; D001284:Atrophy; D001480:Basal Ganglia Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011149:Pons / Q000378:metabolism / Q000473:pathology*; D013494:Supranuclear Palsy, Progressive / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000473:pathology*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D016875:tau Proteins