| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Centre for Aging Brain and Dementia (B.B., A.A., E.P., A.P.), Department of Neurology, University of Brescia; the Centre of Excellence for Neurodegenerative Disorders and Department of Pharmacological Sciences (M.M., F.G., M.D.), University of Milan; the Section of Clinical Neuroscience (L.P., P.C.), University of Perugia; Department of Neurology (U.B.), University of Pisa; Department of Health Sciences (M.G.), Section of Medical Statistics & Epidemiology, University of Pavia; and the Vita-Salute San Raffaele University and Scientific Institute San Raffaele (D.P.), Milan, Italy.
Address correspondence and reprint requests to Dr. Monica Di Luca, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy monica.diluca{at}unimi.it
Objective: In CSF, extended (55 kDa) and truncated (33 kDa) tau forms have been previously recognized, and the tau 33 kDa/55 kDa ratio has been found significantly reduced in progressive supranuclear palsy (PSP) vs in other neurodegenerative disorders. The aim of this study was to evaluate the diagnostic value of the CSF tau form ratio as a biomarker of PSP and to correlate the structural anatomic changes as measured by means of voxel-based morphometry (VBM) to CSF tau form ratio decrease.
Methods: A total of 166 subjects were included in the study (21 PSP, 20 corticobasal degeneration syndrome, 44 frontotemporal dementia, 29 Alzheimer disease, 10 Parkinson disease, 15 dementia with Lewy bodies, and 27 individuals without any neurodegenerative disorder). Each patient underwent a standardized clinical and neuropsychological evaluation. In CSF, a semiquantitative immunoprecipitation was developed to evaluate CSF tau 33 kDa/55 kDa ratio. MRI assessment and VBM analysis was carried out.
Results: Tau form ratio was significantly reduced in patients with PSP (0.504 ± 0.284) when compared to age-matched controls (0.989 ± 0.343), and to patients with other neurodegenerative conditions (range = 0.899–1.215). The area under the curve (AUC) of the receiver operating characteristic analysis in PSP vs other subgroups ranged from 0.863 to 0.937 (PSP vs others, AUC = 0.897, p < 0.0001). VBM study showed that CSF tau form ratio decrease correlated significantly with brainstem atrophy.
Conclusions: Truncated tau production, which selectively affects brainstem neuron susceptibility, can be considered a specific and reliable marker for PSP. Tau form ratio was the lowest in progressive supranuclear palsy with no overlap with any other neurodegenerative illness.
GLOSSARY: AD = Alzheimer disease; AUC = area under the curve; BADL = Basic Activity of Daily Living; CBDS = corticobasal degeneration; CON = controls; DLB = dementia with Lewy bodies; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; FTD = frontotemporal dementia; IADL = Instrumental Activities of Daily Living; MMSE = Mini-Mental State Examination; MSA = multiple system atrophy; PD = Parkinson disease; PSP = progressive supranuclear palsy; ROC = receiver operating characteristic; UPDRS = Unified Parkinson’s Disease Rating Scale; VBM = voxel-based morphometry.
e-Pub ahead of print on October 29, 2008, at www.neurology.org.
*These authors contributed equally.
Supported in part by the EU Grants cNEUPRO (contract LSHM-CT-2007-037950).
Disclosure: The authors report no disclosures.
Received February 16, 2008. Accepted in final form August 29, 2008.
Related Article
Neurology 2008 71: 1754-1755.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
