{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:16:17Z","timestamp":1785474977493,"version":"3.56.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,7,16]]},"abstract":"<jats:p>Background: There are indications for sex-specific differences regarding the association between kallikrein-8 (KLK8) and cognitive impairment in early stages of Alzheimer\u2019s disease for which KLK8 may be an early blood-based biomarker. These may be due to different levels of sex hormones. To correctly interpret KLK8 blood concentrations, sex-specific analyses are needed. Objective: The aim of our exploratory study was to investigate sex-specific differences in blood-based KLK8 in participants of the population-based Heinz Nixdorf Recall study with different cognitive status and the association between KLK8 and sex hormones. Methods: In 290 participants (45% women, 69.7\u00b17.4 years (mean\u00b1SD)) we investigated sex-specific serum KLK8 differences between cognitively unimpaired (CU, 43%) and cognitively impaired (CI) participants and the association between KLK8 and dehydroepiandrosteronsulfate (DHEAS), estradiol and testosterone, using adjusted multiple linear regression. Results: The mean\u00b1SD KLK8 was similar for CU men (808.1\u00b1729.6\u200apg\/ml) and women (795.9\u00b1577.7\u200apg\/ml); adjusted mean-difference [95%-CI]: \u201395.3 [\u2013324.1;133.5] pg\/ml. KLK8 was lower in CI women (783.5\u00b1498.7\u200apg\/ml) than men (1048.4\u00b1829\u200apg\/ml); \u2013261 [\u2013493.1; \u201329] pg\/ml. In men but not women, there was a weak indication for a positive slope between estradiol (11.9 [\u20130.4;24.3] pg\/ml) and DHEAS (1.4 [\u20130.5;3.3] pg\/ml) with KLK8, while testosterone had no impact. Conclusions: The results suggested a different role for KLK8 in the development of cognitive impairment in men and women, potentially influenced by sex hormones. To use blood KLK8 as an early biomarker, further research on hormonal regulation of KLK8 expression is needed as a part of the investigation of the KLK8 involvement in cognitive impairment and Alzheimer's disease pathology.<\/jats:p>","DOI":"10.3233\/jad-240045","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T10:48:43Z","timestamp":1720781323000},"page":"495-507","source":"Crossref","is-referenced-by-count":2,"title":["Sex-Specific Differences in Serum Kallikrein-8 (KLK8): An Exploratory Study"],"prefix":"10.1177","volume":"100","author":[{"given":"Nela","family":"Krizanovic","sequence":"first","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Jokisch","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"J\u00f6ckel","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00f6rge","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Stang","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"},{"name":"Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Schramm","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-240045_ref1","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3389\/fncel.2020.00166","article-title":"Involvement of kallikrein-related peptidases in nervous system disorders","volume":"14","author":"Mella","year":"2020","journal-title":"Front Cell Neurosci"},{"key":"10.3233\/JAD-240045_ref2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1136\/jnnp-2019-321073","article-title":"CSF and blood kallikrein-8: A promising early biomarker for Alzheimer\u2019s disease","volume":"91","author":"Teuber-Hanselmann","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JAD-240045_ref3","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/nan.12687","article-title":"Genetic knockdown of Klk8 has sex-specific multi-targeted therapeutic effects on Alzheimer\u2019s pathology in mice","volume":"47","author":"Herring","year":"2021","journal-title":"Neuropathol Appl Neurobiol"},{"key":"10.3233\/JAD-240045_ref4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s13195-021-00945-x","article-title":"Is kallikrein-8 a blood biomarker for detecting amnestic mild cognitive impairment? 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