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Prior investigations identified vascular-associated TDP-43-positive micro-lesions, known as \u201cLin bodies,\u201d located on or near the brain capillaries of some individuals with LATE-NC. This study aimed to investigate the relationship between the accumulation of Lin bodies and glial cells in LATE-NC and the potential co-localization with ferritin, a protein associated with iron storage. Using multiplexed immunohistochemistry and digital pathology tools, we conducted pathological analyses to investigate the relationship between Lin bodies and glial markers (GFAP for astrocytes, IBA1 for microglia) and ferritin. Analyses were conducted on post-mortem brain tissues collected from individuals with pathologically confirmed Alzheimer\u2019s disease neuropathological changes (ADNC) and LATE-NC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>As shown previously, there was a robust association between Lin bodies and GFAP-positive astrocyte processes. Moreover, we also observed Lin bodies frequently co-localizing with ferritin, suggesting a potential link to compromised vascular integrity. Subsequent analyses demonstrated increased astrocytosis near Lin body-positive vessels compared to those without Lin bodies, particularly in ADNC cases. These results suggest that the accumulation of Lin bodies may elicit an increased glial response, particularly among astrocytes, possibly related to impaired vascular integrity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Lin bodies are associated with a local reactive glial response. The strong association of Lin bodies with ferritin suggests that the loss of vascular integrity may be either a cause or a consequence of the pTDP-43 pathology. The reactive glia surrounding the affected vessels could further compromise vascular function.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40478-024-01826-8","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T09:02:17Z","timestamp":1720774937000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A pathologic study of Perivascular pTDP-43 Lin bodies in LATE-NC"],"prefix":"10.1186","volume":"12","author":[{"given":"Ryan K.","family":"Shahidehpour","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter T.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4646-6757","authenticated-orcid":false,"given":"Adam D.","family":"Bachstetter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"1826_CR1","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1038\/s41374-019-0196-y","volume":"99","author":"Y Chornenkyy","year":"2019","unstructured":"Chornenkyy Y, Fardo DW, Nelson PT (2019) Tau and TDP-43 proteinopathies: kindred pathologic cascades and genetic pleiotropy. 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