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Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["17253"],"award-info":[{"award-number":["17253"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008383","name":"Stichting ParkinsonFonds","doi-asserted-by":"publisher","award":["1881"],"award-info":[{"award-number":["1881"]}],"id":[{"id":"10.13039\/501100008383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Neurodegener"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Increased neurofilament levels in biofluids are commonly used as a proxy for neurodegeneration in several neurodegenerative disorders. In this study, we aimed to investigate the distribution of neurofilaments in the cerebral cortex of Parkinson\u2019s disease (PD), PD with dementia (PDD) and dementia with Lewy bodies (DLB) donors, and its association with pathology load and MRI measures of atrophy and diffusivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a within-subject post-mortem MRI-pathology approach, we included 9 PD, 12 PDD\/DLB and 18 age-matched control donors. Cortical thickness and mean diffusivity (MD) metrics were extracted respectively from 3DT1 and DTI at 3T in-situ MRI. After autopsy, pathological hallmarks (pSer129-\u03b1Syn, p-tau and amyloid-\u03b2 load) together with neurofilament light-chain (NfL) and phosphorylated-neurofilament medium- and heavy-chain (p-NfM\/H) immunoreactivity were quantified in seven cortical regions, and studied in detail with confocal-laser scanning microscopy. The correlations between MRI and pathological measures were studied using linear mixed models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to controls, p-NfM\/H immunoreactivity was increased in all cortical regions in PD and PDD\/DLB, whereas NfL immunoreactivity was increased in the parahippocampal and entorhinal cortex in PDD\/DLB. NfL-positive neurons showed degenerative morphological features and axonal fragmentation. The increased p-NfM\/H correlated with p-tau load, and NfL correlated with pSer129-\u03b1Syn but more strongly with p-tau load in PDD\/DLB. Lastly, neurofilament immunoreactivity correlated with cortical thinning in PD and with increased cortical MD in PDD\/DLB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, increased neurofilament immunoreactivity suggests underlying axonal injury and neurofilament accumulation in morphologically altered neurons with increased pathological burden. Importantly, we demonstrate that such neurofilament markers at least partly explain MRI measures that are associated with the neurodegenerative process.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s40035-022-00328-8","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T04:48:41Z","timestamp":1674190121000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson\u2019s disease dementia"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-2862","authenticated-orcid":false,"given":"Irene","family":"Frigerio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max A.","family":"Laansma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Pei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma J. 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