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It has been reported that these patients also experience sleep disturbances, which might implicate a disturbed circadian rhythm of the sleep\/wake cycle. It remains unknown, however, whether cells involved in the circadian sleep\/wake cycle are affected by ALS- and FTLD-related neuropathological changes including phosphorylated TDP-43 (pTDP-43) aggregates and dipeptide repeat protein (DPR) inclusions resulting from the <jats:italic>C9orf72<\/jats:italic> hexanucleotide repeat expansion. Immunohistochemistry for DPR and pTDP-43 pathology was performed in post-mortem hypothalamus and pineal gland tissue of patients with ALS and\/or FTLD-TDP with and without the <jats:italic>C9orf72<\/jats:italic> repeat expansion and healthy controls. Circadian sleep\/wake-associated cells, including pinealocytes and hypothalamic neurons related to the suprachiasmatic nucleus (SCN), were microscopically assessed. We observed numerous DPR inclusions (poly(GA), poly(GP), poly(GR) and poly(PR)) in the pinealocytes and few poly(GA) inclusions in the SCN-related neurons in <jats:italic>C9orf72-<\/jats:italic>related ALS and\/or FTLD-TDP cases. These circadian sleep\/wake-associated cells, however, were devoid of pTDP-43 pathology both in <jats:italic>C9orf72-<\/jats:italic> and non<jats:italic>C9orf72-<\/jats:italic>related ALS and\/or FTLD-TDP cases. Our neuropathological findings show that pinealocytes and, to a lesser extent, SCN-related neurons are affected by DPR pathology. This may reflect an involvement of these cells in sleep\/wake disturbances observed in ALS and\/or FTLD-TDP patients.<\/jats:p>","DOI":"10.1186\/s40478-019-0845-9","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T10:09:09Z","timestamp":1575281349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Circadian sleep\/wake-associated cells show dipeptide repeat protein aggregates in C9orf72-related ALS and FTLD cases"],"prefix":"10.1186","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0545-8072","authenticated-orcid":false,"given":"Lieselot","family":"Dedeene","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelien","family":"Van Schoor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik","family":"Vandenberghe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Van Damme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koen","family":"Poesen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietmar Rudolf","family":"Thal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,2]]},"reference":[{"key":"845_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.smrv.2015.05.007","volume":"26","author":"RM Ahmed","year":"2016","unstructured":"Ahmed RM, Newcombe REA, Piper AJ, Lewis SJ, Yee BJ, Kiernan MC, Grunstein RR (2016) Sleep disorders and respiratory function in amyotrophic lateral sclerosis. 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Ethical approval for the use of tissue from these cases for this study was granted by the UZ\/KU-Leuven ethical committee (Belgium) (S60803).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable for this study, which did not use person\u2019s data. Only anonymized or pseudonymized data were processed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"RV\u2019s institution has a clinical trial agreement (RV as PI) with AbbVie (USA), Biogen (USA), Genentech (USA), Novartis (Switzerland), and Roche (Switzerland). PVD participated in advisory board meetings for Genzyme (USA), Pfizer (USA), Biogen (USA), Cytokinetics (USA), Mitsubishi Tanabe (Japan), CSL Behring (USA), Alexion Pharmaceuticals (USA). DRT received speaker honorary from Novartis Pharma AG (Switzerland), travel reimbursement from GE-Healthcare (UK) and UCB (BE), and collaborated with Novartis Pharma AG (Switzerland), Probiodrug (Germany), GE-Healthcare (UK), and Janssen Pharmaceutical Companies (Belgium).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"189"}}