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Ann Neurol. 2017 Aug;82(2):247-258. doi: 10.1002/ana.24996. Epub 2017 Aug 19.

Ante mortem cerebrospinal fluid tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration.

Author information

1
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
2
Frontotemporal Degeneration Center, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
3
Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau, Barcelona, Spain and Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, CIBERNED, Barcelona, Spain.
4
Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
5
Alzheimer's Disease Center, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
6
Translational Neuropathology Lab, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

Abstract

OBJECTIVE:

To test the hypotheses that (1) antemortem cerebrospinal fluid (CSF) tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration (FTLD) and (2) tauopathy patients have higher phosphorylated-tau levels compared to transactivation response element DNA-binding protein 43 (TDP-43) proteinopathy patients while accounting for Alzheimer's disease (AD) copathology.

METHODS:

Patients had autopsy-confirmed FTLD with tauopathy (n = 31), TDP-43 proteinopathy (n = 49), or AD (n = 26) with antemortem CSF. CSF tau levels were compared between groups and correlated with digital histology measurement of postmortem tau pathology averaged from three cerebral regions (angular gyrus, mid-frontal cortex, and anterior cingulate gyrus). Multivariate linear regression tested the association of ante mortem CSF tau levels with postmortem tau pathology adjusting for demographics.

RESULTS:

Multivariate regression found an independent association of ante mortem CSF phosphorylated tau levels with postmortem cerebral tau pathology in FTLD (Beta = 1.3; 95% confidence interval = 0.2-2.4; p < 0.02). After excluding patients with coincident AD-associated tau pathology accompanying sporadic FTLD, we found lower CSF phosphorylated tau levels in the TDP-43 group (median = 7.4pg/ml; interquartile range [IQR] = 6.0, 12.3; n = 26) compared to the tauopathy group (median = 12.5pg/ml; IQR = 10.7, 15.0; n = 23; Z = 2.6; p < 0.01).

INTERPRETATION:

CSF phosphorylated-tau levels are positively associated with cerebral tau burden in FTLD. In vivo detection of AD copathology in sporadic FTLD patients may help stratify clinical cohorts with pure neuropathology in which low CSF phosphorylated-tau levels may have diagnostic utility to distinguish TDP-43 proteinopathy from tauopathy. Autopsy-confirmed samples are critical for FTLD biomarker development and validation. Ann Neurol 2017;82:247-258.

PMID:
28719018
PMCID:
PMC5776747
DOI:
10.1002/ana.24996
[Indexed for MEDLINE]
Free PMC Article

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