A Combination of CSF Tau Ratio and Midsaggital Midbraintopons Atrophy for the Early Diagnosis of Progressive Supranuclear Palsy

Article type: Research Article

Authors: Borroni, Barbara^{a; *} | Malinverno, Matteo^b | Gardoni, Fabrizio^b | Grassi, Mario^c | Parnetti, Lucilla^d | Agosti, Chiara^a | Alberici, Antonella^a | Premi, Enrico^a | Bonuccelli, Ubaldo^e | Gasparotti, Roberto^f | Calabresi, Paolo^{d; e} | Di Luca, Monica^b | Padovani, Alessandro^a

Affiliations: [a] The Centre for Aging Brain and Dementia, Department of Neurology, University of Brescia, Brescia, Italy | [b] The Centre of Excellence for Neurodegenerative Disorders and Department of Pharmacological Sciences, University of Milan, Milan, Italy | [c] Department of Health Sciences, Section of Medical Statistics & Epidemiology, University of Pavia, Italy | [d] The Section of Clinical Neuroscience, University of Perugia, Perugia, Italy | [e] IRCCS Fondazione S. Lucia, Rome, Italy | [f] Neuroradiology Unit, University of Brescia, Brescia, Italy

Correspondence: [*] Correspondence to: Barbara Borroni, MD, Department of Neurology, University of Brescia, Piazza Spedali Civili 1, 20125 Brescia, Italy. Tel.: +39 030 3995632; Fax: +39 030 3995027; E-mail: [email protected].

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=CSF Tau ratio3×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.

Keywords: Biological marker, cerebrospinal fluid, corticobasal syndrome, frontotemporal dementia, MRI, progressive supranuclear palsy, tau

DOI: 10.3233/JAD-2010-100333

Journal: Journal of Alzheimer's Disease, vol. 22, no. 1, pp. 195-203, 2010