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Despite previous\u00a0studies in several neurodegenerative disorders, their status in frontotemporal lobar degeneration (FTLD) remains\u00a0unexplored. Our study aims to characterize wasteosomes\u00a0in the three primary FTLD proteinopathies, assessing frequency, distribution, protein detection, and association with aging or disease duration. Wasteosome\u00a0scores were obtained in various brain regions from 124 post-mortem\u00a0diagnosed sporadic FTLD patients, including 75 participants with tau (FTLD-tau), 42 with TAR DNA-binding protein 43 (FTLD-TDP), and 7 with Fused in Sarcoma (FTLD-FUS) proteinopathies, along with 29 control subjects. The\u00a0wasteosome amount in each brain region for the different FLTD patients was assessed with a permutation test with age at death and sex as covariables, and multiple regressions explored associations with age at death and disease duration. Double immunofluorescence studies examined altered proteins linked to FTLD in wasteosomes. FTLD patients showed a higher accumulation of wasteosomes\u00a0than control subjects, especially those with FTLD-FUS. Unlike FTLD-TDP and control subjects, wasteosome\u00a0accumulation did not increase with age in FTLD-tau and FTLD-FUS. Cases with shorter disease duration in FTLD-tau and FTLD-FUS seemed to exhibit higher wasteosome quantities, whereas FTLD-TDP appeared to show an increase with disease progression. Immunofluorescence studies revealed the presence of tau and phosphorylated-TDP-43 in the periphery of isolated wasteosomes\u00a0in some patients with FTLD-tau and FTLD-TDP, respectively. Central inclusions of FUS were observed\u00a0in a higher number of wasteosomes in FTLD-FUS patients. These findings suggest a role of wasteosomes\u00a0in FTLD, especially in the more aggressive forms of FLTD-FUS. Detecting these proteins, particularly FUS, in wasteosomes from cerebrospinal fluid could be a potential biomarker for FTLD.<\/jats:p>","DOI":"10.1186\/s40478-024-01812-0","type":"journal-article","created":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T00:02:03Z","timestamp":1718409723000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Increase in wasteosomes (corpora amylacea) in frontotemporal lobar degeneration with specific detection of tau, TDP-43 and FUS pathology"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-1703","authenticated-orcid":false,"given":"Raquel","family":"Alsina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-9791","authenticated-orcid":false,"given":"Marta","family":"Riba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-9792","authenticated-orcid":false,"given":"Agn\u00e8s","family":"P\u00e9rez-Millan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2557-0010","authenticated-orcid":false,"given":"Sergi","family":"Borrego-\u00c9cija","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5774-7453","authenticated-orcid":false,"given":"Iban","family":"Aldecoa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8233-9838","authenticated-orcid":false,"given":"Clara","family":"Romera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1795-4228","authenticated-orcid":false,"given":"Mircea","family":"Balasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3286-8459","authenticated-orcid":false,"given":"Anna","family":"Antonell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5066-4150","authenticated-orcid":false,"given":"Albert","family":"Llad\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-0104","authenticated-orcid":false,"given":"Yaroslau","family":"Compta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-8244","authenticated-orcid":false,"given":"Jaume","family":"del Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7750-896X","authenticated-orcid":false,"given":"Raquel","family":"S\u00e1nchez-Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7734-1546","authenticated-orcid":false,"given":"Carme","family":"Pelegr\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-8578","authenticated-orcid":false,"given":"Laura","family":"Molina-Porcel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2113-238X","authenticated-orcid":false,"given":"Jordi","family":"Vilaplana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,15]]},"reference":[{"key":"1812_CR1","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1038\/s41598-018-38010-7","volume":"9","author":"E Aug\u00e9","year":"2019","unstructured":"Aug\u00e9 E, Bechmann I, Llor N, Vilaplana J, Krueger M, Pelegr\u00ed C (2019) Corpora amylacea in human hippocampal brain tissue are intracellular bodies that exhibit a homogeneous distribution of neo-epitopes. 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