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

Abstract

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.