Sex hormone-binding globulin (Shbg) in cerebrospinal fluid does not discriminate between the main ftld pathological subtypes but correlates with cognitive decline in ftld tauopathies

Marta Del Campo, Yolande A.L. Pijnenburg, Alice Chen-Plotkin, David J. Irwin, Murray Grossman, Harry A.M. Twaalfhoven, William T. Hu, Lieke H. Meeter, John van Swieten, Lisa Vermunt, Frans Martens, Annemieke C. Heijboer, Charlotte E. Teunissen

Publication Date: 10/01/2021

Abstract: Biomarkers to discriminate the main pathologies underlying frontotemporal lobar degeneration (FTLD-Tau, FTLD-TDP) are lacking. Our previous FTLD cerebrospinal fluid (CSF) proteome study revealed that sex hormone-binding globulin (SHBG) was specifically increased in FTLD-Tau patients. Here we investigated the potential of CSF SHBG as a novel biomarker discriminating the main FTLD pathological subtypes. SHBG was measured in CSF samples from patients with FTLD-Tau (n = 23), FTLD-TDP (n = 29) and controls (n = 33) using an automated electro-chemiluminescent immunoassay. Differences in CSF SHBG levels across groups, as well as its association with CSF YKL40, pTau181/total-Tau ratio and cognitive function were analyzed. CSF SHBG did not differ across groups, though a trend towards elevated levels in FTLD-Tau cases compared to FTLD-TDP and controls was observed. CSF SHBG levels were not associated with either CSF YKL40 or the p/tTau ratio. They, however, inversely correlated with the MMSE score (r = −0.307, p = 0.011), an association likely driven by the FTLD-Tau group (r FTLD-Tau = −0.38; r FTLD-TDP = −0.02). CSF SHBG is not a suitable biomarker to discriminate FTLD-Tau from FTLD-TDP.