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Sex differences in CSF biomarkers vary by Alzheimer's disease stage and APOE ε4 genotype

Mofrad, RB; Tijms, BM; Scheltens, P; Barkhof, F; van der Flier, WM; Am Sikkes, S; Teunissen, CE; (2020) Sex differences in CSF biomarkers vary by Alzheimer's disease stage and APOE ε4 genotype. Neurology , 95 (17) e2378-e2388. 10.1212/WNL.0000000000010629. Green open access

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Abstract

OBJECTIVE: To evaluate sex-differences in cerebrospinal fluid (CSF) biomarkers, taking the potential modifying role of clinical disease stage and APOE-e4 genotype into account. METHOD: We included participants (n=1801) with probable AD dementia (n=937), Mild Cognitive Impairment (MCI; n=437) and Subjective Cognitive Decline (SCD; n=427). Main outcomes were CSF amyloid β1-42 (Aβ42), total tau (t-Tau) and tau phosphorylated at threonine 181 (p-Tau) levels. Age corrected three-way interactions between sex, disease stage (i.e. syndrome diagnosis at baseline) and APOE-e4 were tested with linear regression analyses for each outcome measure. In case of significant interactions (p<0.05), sex-differences were further evaluated by stratifying analyses for clinical disease stage and APOE-e4 genotype including age as a covariate. RESULTS: Three-way interactions were significant for total Tau (p<0.001) and p-Tau (p<0.01), but not Aβ42. In APOE-e4 carriers, women showed higher (p)Tau concentrations than men in SCD (Cohens d (95%CI): t-Tau= 0.52 (0.19-0.84), p<.001; p-Tau=0.44 (0.11-0.77) p=.004 ) and MCI (Cohens d (95%CI): t-Tau= 0.54 (0.28-0.80), p<.001; p-Tau=0.52 (0.26-0.77),p<.001), but not in AD dementia. In APOE-e4 non-carriers, women showed higher (p)Tau concentrations in MCI (Cohens d (95%CI): t-Tau= 0.49 (0.17-0.80), p=.002; p-Tau=0.47 (0.16-0.78), p=.003) and AD dementia (Cohens d (95%CI): t-Tau= 0.42 (0.19-0.65), p<.001; p-Tau=0.38 (0.15-0.61) p=.002), but not in SCD. CONCLUSIONS: Within APOE-e4 carriers, sex-differences in CSF (p)Tau are more evident in early disease stages, whereas for APOE-e4 non carriers sex-differences are more evident in advanced disease stages. These findings suggest that the effect of APOE-e4 on sex-differences in CSF biomarkers depends on disease stage in AD.

Type: Article
Title: Sex differences in CSF biomarkers vary by Alzheimer's disease stage and APOE ε4 genotype
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000010629
Publisher version: http://dx.doi.org/10.1212/WNL.0000000000010629
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/10109310
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