“Tau forms in CSF as a reliable biomarker” for PSP

This is a GREAT Italian study (just published last week) on the use of CSF (cerebrospinal fluid) in diagnosing PSP. The researchers found: “Truncated tau production, which selectively affects brainstem neuron susceptibility, can be considered a specific and reliable marker for PSP.”

“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.” Researchers concluded that “Tau form ratio was the lowest in progressive supranuclear palsy with no overlap with any other neurodegenerative illness.”

If this can be duplicated and if the clinical diagnoses of the 166 subjects involved in the study can be confirmed on post-mortem analysis, we will have a biomarker for diagnosing PSP.

I’m pretty sure this is the paper that Dr. Golbe was referring to in the PSP/CBD webinar a few weeks ago.

Robin

Neurology. 2008 Oct 29. [Epub ahead of print]

Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy.

Borroni B, Malinverno M, Gardoni F, Alberici A, Parnetti L, Premi E, Bonuccelli U, Grassi M, Perani D, Calabresi P, Di Luca M, Padovani A.

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.

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.

PubMed ID#: 18971445 (see pubmed.gov for abstract only)