{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:29:47Z","timestamp":1792074587159,"version":"4.4.0"},"reference-count":67,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,4,10]],"date-time":"2018-04-10T00:00:00Z","timestamp":1523318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HE 6823\/3\u20101"],"award-info":[{"award-number":["HE 6823\/3\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KE 1134\/7\u20101"],"award-info":[{"award-number":["KE 1134\/7\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Women seem to have a higher vulnerability to Alzheimer's disease (AD), but the underlying mechanisms of this sex dichotomy are not well understood. Here, we first determined the influence of sex on various aspects of Alzheimer's pathology in transgenic CRND8 mice. We demonstrate that beta\u2010amyloid (A\u03b2) plaque burden starts to be more severe around P180 (moderate disease stage) in female transgenics when compared to males and that aging aggravates this sex\u2010specific difference. Furthermore, we show that female transgenics suffer from higher levels of neurovascular dysfunction around P180, resulting in impaired A\u03b2 peptide clearance across the blood\u2010brain\u2010barrier at P360. Female transgenics show also higher levels of diffuse microgliosis and inflammation, but the density of microglial cells surrounding A\u03b2 plaques is less in females. In line with this finding, testosterone compared to estradiol was able to improve microglial viability and A\u03b2 clearance\n                    <jats:italic>in vitro<\/jats:italic>\n                    . The spatial memory of transgenics was in general poorer than in wildtypes and at P360 worse in females irrespective of their genotype. This difference was accompanied by a slightly diminished dendritic complexity in females. While all the above\u2010named sex\u2010differences emerged after the onset of A\u03b2 pathology, kallikrein\u20108 (KLK8) protease levels were, as an exception, higher in female than in male brains very early when virtually no plaques were detectable. In a second step, we quantified cerebral KLK8 levels in AD patients and healthy controls, and could ascertain, similar to mice, higher KLK8 levels not only in AD\u2010affected but also in healthy brains of women. Accordingly, we could demonstrate that estradiol but not testosterone induces KLK8 synthesis in neuronal and microglial cells. In conclusion, multiple features of AD are more pronounced in females. Here, we show for the first time that this sex\u2010specific difference may be meditated by estrogen\u2010induced KLK8 overproduction long before AD pathology emerges.\n                  <\/jats:p>","DOI":"10.1111\/bpa.12599","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T09:42:56Z","timestamp":1520242976000},"page":"947-964","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Higher levels of kallikrein\u20108 in female brain may increase the risk for Alzheimer's disease"],"prefix":"10.1111","volume":"28","author":[{"given":"Kathy","family":"Keyvani","sequence":"first","affiliation":[{"name":"Institute of Neuropathology University of Duisburg\u2010Essen, Hufelandstr. 55  45122 Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"M\u00fcnster","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology University of 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Hufelandstr. 55  45122 Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Karout","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology University of Duisburg\u2010Essen, Hufelandstr. 55  45122 Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Hammesfahr","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology University of Duisburg\u2010Essen, Hufelandstr. 55  45122 Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Duisburg\u2010Essen, Hufelandstr. 55  45122 Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk M.","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Duisburg\u2010Essen, Hufelandstr. 55  45122 Essen 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