{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:38:03Z","timestamp":1791520683600,"version":"4.3.4"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Leif Lundblad Family"},{"name":"Olle Engkvist Foundation"},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Amyloid-\u03b2 (A\u03b2) accumulation is a hallmark of Alzheimer\u2019s disease. Cerebral A\u03b2 deposition is attenuated by a functional glymphatic system, in which perivascular entry of CSF and its exchange with interstitial fluid mediate solute clearance. Parenchymal border macrophages (PBMs), positioned along glymphatic pathways, are emerging as important players for glymphatic clearance. However, how glymphatic function and PBMs are affected in App knock-in models of Alzheimer\u2019s disease is unknown.<\/jats:p>\n                  <jats:p>In this study, we used two App knock-in mouse models that develop progressive A\u03b2 pathology, AppNL-F and AppNL-G-F. AppNL-F mice showed reductions in glymphatic influx and clearance at 6 months, preceding substantial A\u03b2 plaque deposition. The decrease in glymphatic function in AppNL-F mice was correlated with a loss of PBMs and altered marker expression. Acute administration of A\u03b2 into the CSF decreased the number of PBMs and impaired glymphatic transport in wild-type mice, thus recapitulating the pre-plaque stage. In contrast, the number of PBMs was not reduced in AppNL-G-F mice, possibly owing to an enhanced A\u03b2 phagocytic capacity in PBMs. Four weeks of systemic anti-A\u03b2 antibody treatment efficiently reduced A\u03b2 plaque load and rescued PBMs in some brain regions; however, the treatment did not restore glymphatic function in the AppNL-F model.<\/jats:p>\n                  <jats:p>These findings suggest that glymphatic dysfunction in App knock-in models of Alzheimer\u2019s disease is not driven by parenchymal A\u03b2 plaque load but is closely linked to pre-plaque A\u03b2-induced loss of PBMs. Preservation of PBM abundance and their normal marker expression might be important for maintaining glymphatic function and mitigating early progression of Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awag080","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T12:43:59Z","timestamp":1772109839000},"page":"2422-2437","source":"Crossref","is-referenced-by-count":10,"title":["Early glymphatic failure in\n                    <i>AppNL-F<\/i>\n                    knock-in mice is linked to parenchymal border macrophages loss"],"prefix":"10.1093","volume":"149","author":[{"given":"Na","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Experimental Medical Science, Lund University , Lund 22184 ,","place":["Sweden"]},{"name":"Wallenberg Centre for Molecular Medicine, Lund University , Lund 22184 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University , Lund 22184 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1610-7040","authenticated-orcid":false,"given":"Marios","family":"Kritsilis","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University , Lund 22184 ,","place":["Sweden"]},{"name":"Wallenberg Centre for Molecular Medicine, Lund University , Lund 22184 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley M","family":"Swanberg","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University , Lund 22184 ,","place":["Sweden"]},{"name":"Wallenberg Centre for Molecular Medicine, Lund University , Lund 22184 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University , Lund 22184 ,","place":["Sweden"]},{"name":"Wallenberg Centre for Molecular Medicine, Lund University , Lund 22184 ,","place":["Sweden"]},{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanhui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University , Lund 22184 ,","place":["Sweden"]},{"name":"Wallenberg Centre for Molecular Medicine, Lund University , Lund 22184 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brecht","family":"Moonen","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University , Lund 22184 ,","place":["Sweden"]},{"name":"Wallenberg Centre for Molecular Medicine, Lund University , Lund 22184 ,","place":["Sweden"]},{"name":"Department of Immunology and Infection, Biomedical Research Institute, Hasselt University , Diepenbeek 3590 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Deierborg","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University , Lund 22184 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , Stockholm 17177 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stina","family":"Syv\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Public Health and Caring Sciences, Uppsala University , Uppsala 75185 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