{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:47:49Z","timestamp":1792802869128,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002869","name":"Christian-Albrechts-Universit\u00e4t zu Kiel","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002869","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Genetic variants in\n                    <jats:italic>TMEM106B<\/jats:italic>\n                    are a major risk factor for several neurodegenerative diseases including frontotemporal degeneration, limbic\u2010predominant age\u2010related TDP\u201043 encephalopathy, Parkinson's disease, late\u2010onset\u2010Alzheimer's disease and constitute a genetic determinant of differential aging.\n                    <jats:italic>TMEM106B<\/jats:italic>\n                    encodes an integral lysosomal membrane protein but its precise physiological function in the central nervous system remains enigmatic. Presently, we aimed to increase understanding of TMEM106B contribution to general brain function and aging. We analyzed an aged cohort of\n                    <jats:italic>Tmem106b<\/jats:italic>\n                    knockout\u2010, heterozygote and wild\u2010type mice in a behavioral test battery including assessments of motor function as well as, social, emotional and cognitive function. Aged\n                    <jats:italic>Tmem106b<\/jats:italic>\n                    knockout (KO) mice displayed diverse behavioral deficits including motor impairment, gait defects and reduced startle reactivity. In contrast, no prominent deficits were observed in social, emotional or cognitive behaviors. Histologically, we observed late\u2010onset loss of Purkinje cells followed by reactive gliosis in the cerebellum, which likely contributed to progressive decline in motor function and gait defects in particular. Reactive gliosis was not restricted to the cerebellum but observed in different areas of the brain including the brain stem and parts of the cerebral cortex. Surviving Purkinje cells showed vacuolated lysosomes in the axon initial segment, implicating TMEM106B\u2010dependent lysosomal trafficking defects as the underlying cause of axonal and more general neuronal dysfunction contributing to behavioral impairments. Our experiments help to elucidate how TMEM106B affects spatial neuronal homeostasis and exemplifies a critical role of TMEM106B in neuronal cells for survival.\n                  <\/jats:p>","DOI":"10.1111\/bpa.12903","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T08:41:37Z","timestamp":1601887297000},"page":"223-238","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Aged\n                    <i>Tmem106b<\/i>\n                    knockout mice display gait deficits in coincidence with Purkinje cell loss and only limited signs of non\u2010motor dysfunction"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-824X","authenticated-orcid":false,"given":"Stijn","family":"Stroobants","sequence":"first","affiliation":[{"name":"Laboratory of Biological Psychology KU Leuven  Tiensestraat 102 Leuven 3000 Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2243-2106","authenticated-orcid":false,"given":"Rudi","family":"D\u2019Hooge","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Psychology KU Leuven  Tiensestraat 102 Leuven 3000 Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9699-9351","authenticated-orcid":false,"given":"Markus","family":"Damme","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie Christian\u2010Albrechts\u2010Universit\u00e4t zu Kiel  Kiel 24098 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.12.022"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.18"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0619-9"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1849794"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1361-4"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa154"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31820a0e3b"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1239-x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws006"},{"key":"e_1_2_11_11_1","first-page":"845","article-title":"Common 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