{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:04:10Z","timestamp":1785409450966,"version":"3.56.0"},"posted":{"date-parts":[[2025,12,5]]},"group-title":"Neuroscience","reference-count":29,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["AG078407"],"award-info":[{"award-number":["AG078407"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["OD011092"],"award-info":[{"award-number":["OD011092"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NS104161"],"award-info":[{"award-number":["NS104161"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Research Foundation - Flanders","award":["1156626N"],"award-info":[{"award-number":["1156626N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Neuronal ceroid lipofuscinosis type 7 (CLN7) is a devastating paediatric neurodegenerative disorder with no cure and limited natural history data to guide therapeutic development. Here, we present the first multimodal characterization of prodromal and early-stage CLN7 disease in Japanese macaques carrying a spontaneous\n                  <jats:italic>CLN7<\/jats:italic>\n                  <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  mutation.\n                <\/jats:p>\n                <jats:p>\n                  Using structural T\n                  <jats:sub>2<\/jats:sub>\n                  -weighted MRI for volumetry, [\n                  <jats:sup>18<\/jats:sup>\n                  F]FDG PET for glucose metabolism, and [\n                  <jats:sup>11<\/jats:sup>\n                  C]PBR28 PET for neuroinflammation, we observed region-dependent patterns in volumetric, molecular, and metabolic alterations.\n                <\/jats:p>\n                <jats:p>\n                  MRI confirmed the presence of disease-associated atrophy in many cortical and subcortical brain regions, consistent with human pathology, [\n                  <jats:sup>18<\/jats:sup>\n                  F]FDG PET revealed early cortical and subcortical widespread hypometabolism, and [\n                  <jats:sup>11<\/jats:sup>\n                  C]PBR28 PET imaging detected progressive neuroinflammation in the same brain areas. CSF analyses further showed age-dependent increases in neurofilament light (NfL), providing convergent evidence for neurodegeneration.\n                <\/jats:p>\n                <jats:p>Together, these results define a prodromal trajectory in CLN7 disease, establish sensitive imaging and fluid biomarkers, and validate the macaque model as a powerful platform for testing interventions.<\/jats:p>","DOI":"10.64898\/2025.12.02.691930","type":"posted-content","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:46:44Z","timestamp":1765198004000},"source":"Crossref","is-referenced-by-count":0,"title":["Prodromal pathogenesis of CLN7 Batten Disease revealed by multimodal biomarkers in macaques"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-1882","authenticated-orcid":false,"given":"William A","family":"Liguore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winde","family":"Hilven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8894-5338","authenticated-orcid":false,"given":"Lili","family":"Lurye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1533-9504","authenticated-orcid":false,"given":"Jordy","family":"Akkermans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7745-8188","authenticated-orcid":false,"given":"Marion","family":"Decrop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-6551","authenticated-orcid":false,"given":"Larry S.","family":"Sherman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4816-7569","authenticated-orcid":false,"given":"Jodi L","family":"McBride","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4205-5432","authenticated-orcid":false,"given":"Daniele","family":"Bertoglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1821-8193","authenticated-orcid":false,"given":"Alison R","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025120913350781000_2025.12.02.691930v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.04.027"},{"key":"2025120913350781000_2025.12.02.691930v1.2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj9608"},{"key":"2025120913350781000_2025.12.02.691930v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(88)80075-5"},{"key":"2025120913350781000_2025.12.02.691930v1.4","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.01369"},{"key":"2025120913350781000_2025.12.02.691930v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.05.011"},{"key":"2025120913350781000_2025.12.02.691930v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70261"},{"key":"2025120913350781000_2025.12.02.691930v1.7","doi-asserted-by":"publisher","DOI":"10.1080\/21678707.2019.1684258"},{"key":"2025120913350781000_2025.12.02.691930v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.04.008"},{"key":"2025120913350781000_2025.12.02.691930v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.05.014"},{"key":"2025120913350781000_2025.12.02.691930v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.11.014"},{"key":"2025120913350781000_2025.12.02.691930v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.05.014"},{"key":"2025120913350781000_2025.12.02.691930v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114381"},{"key":"2025120913350781000_2025.12.02.691930v1.13","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A6726"},{"key":"2025120913350781000_2025.12.02.691930v1.14","unstructured":"MedlinePlus. CLN7 disease Bethesda (MD): National Library of Medicine (US); 2021 [cited 2025 08 Jan 2025]. Available from: https:\/\/medlineplus.gov\/genetics\/condition\/cln7-disease\/."},{"key":"2025120913350781000_2025.12.02.691930v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.07.001"},{"key":"2025120913350781000_2025.12.02.691930v1.16","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-024-03448-8"},{"key":"2025120913350781000_2025.12.02.691930v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq381"},{"key":"2025120913350781000_2025.12.02.691930v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.07.017"},{"key":"2025120913350781000_2025.12.02.691930v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/ajp.20054"},{"key":"2025120913350781000_2025.12.02.691930v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.06.003"},{"key":"2025120913350781000_2025.12.02.691930v1.21","doi-asserted-by":"publisher","DOI":"10.1177\/030098588402100108"},{"key":"2025120913350781000_2025.12.02.691930v1.22","doi-asserted-by":"publisher","DOI":"10.1258\/002367783781070902"},{"key":"2025120913350781000_2025.12.02.691930v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.07.013"},{"key":"2025120913350781000_2025.12.02.691930v1.24","unstructured":"Renner L , Stoddard J , Woolard H , Neuringer M , McGill TJ . Longitudinal Characterization of Retinal Degeneration in a Non-Human Primate Model of CLN7 Batten Disease. Retinal Degeneration; September; Prague, CZ2025."},{"key":"2025120913350781000_2025.12.02.691930v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117517"},{"key":"2025120913350781000_2025.12.02.691930v1.26","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.7b00460"},{"key":"2025120913350781000_2025.12.02.691930v1.27","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13593"},{"key":"2025120913350781000_2025.12.02.691930v1.28","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17269"},{"key":"2025120913350781000_2025.12.02.691930v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104314"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2025.12.02.691930","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T21:35:16Z","timestamp":1765316116000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2025.12.02.691930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":29,"URL":"https:\/\/doi.org\/10.64898\/2025.12.02.691930","relation":{},"subject":[],"published":{"date-parts":[[2025,12,5]]},"subtype":"preprint"}}