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Ante mortem cerebrospinal fluid tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration
Author(s) -
Irwin David J.,
Lleó Alberto,
Xie Sharon X.,
McMillan Corey T.,
Wolk David A.,
Lee Edward B.,
Van Deerlin Viviana M.,
Shaw Leslie M.,
Trojanowski John Q.,
Grossman Murray
Publication year - 2017
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24996
Subject(s) - tauopathy , frontotemporal lobar degeneration , pathology , neuropathology , medicine , autopsy , cerebrospinal fluid , frontotemporal dementia , postmortem studies , hippocampal sclerosis , dementia , temporal lobe , disease , neurodegeneration , psychiatry , epilepsy
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