Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration
| العنوان: | Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration |
|---|---|
| المؤلفون: | Antoine Leuzy, Simon Lovestone, Claire Troakes, Dag Aarsland, Kina Höglund, Michael Schöll, Yau Mun Lim, Abdul Hye, Tibor Hortobágyi, Kaj Blennow, Henrik Zetterberg, Nicholas J. Ashton |
| المصدر: | Acta Neuropathologica Communications, Vol 7, Iss 1, Pp 1-11 (2019) Acta Neuropathologica Communications Ashton, N J, Leuzy, A, Lim, Y M, Troakes, C, Hortobagyi, T, Höglund, K, Aarsland, D, Lovestone, S, Schöll, M, Blennow, K, Zetterberg, H & Hye, A 2019, ' Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration ', Acta Neuropathologica Communications, vol. 7, no. 1 . https://doi.org/10.1186/s40478-018-0649-3Test |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Neurology, Post-mortem, Blood biomarkers, lcsh:RC346-429, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cerebrospinal fluid, Gyrus, Alzheimer Disease, Neurofilament Proteins, medicine, Humans, Longitudinal Studies, Cognitive decline, Neurofilament light chain, Pathological, lcsh:Neurology. Diseases of the nervous system, Aged, Aged, 80 and over, business.industry, Research, Neurodegeneration, Brain, Neurofibrillary Tangles, Neurofibrillary tangle, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Braak, Female, Neurology (clinical), Tau, business, 030217 neurology & neurosurgery, Braak staging |
| الوصف: | Alzheimer’s disease (AD) is pathologically characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles and widespread neuronal loss in the brain. In recent years, blood biomarkers have emerged as a realistic prospect to highlight accumulating pathology for secondary prevention trials. Neurofilament light chain (NfL), a marker of axonal degeneration, is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. A strong relationship with cerebrospinal fluid (CSF) NfL suggests that these biomarker modalities reflect the same pathological process. Yet, the connection between blood NfL and brain tissue pathology has not been directly compared. In this study, longitudinal plasma NfL from cognitively healthy controls (n = 12) and AD participants (n = 57) were quantified by the Simoa platform. On reaching post-mortem, neuropathological assessment was performed on all participants, with additional frozen and paraffin-embedded tissue acquired from 26 participants for further biochemical (Aβ1–42, Aβ1–40, tau) and histological (NfL) evaluation. Plasma NfL concentrations were significantly increased in AD and correlated with cognitive decline, independent of age. Retrospective stratification based on Braak staging revealed that baseline plasma NfL concentrations were associated with higher neurofibrillary tangle pathology at post-mortem. Longitudinal increases in plasma NfL were observed in all Braak groupings; a significant negative association, however, was found between plasma NfL at time point 1 and both its rate of change and annual percentage increase. Immunohistochemical evaluation of NfL in the medial temporal gyrus (MTG) demonstrated an inverse relationship between Braak stages and NfL staining. Importantly, a significant negative correlation was found between the plasma NfL measurement closest to death and the level of NfL staining in the MTG at post-mortem. For the first time, we demonstrate that plasma NfL associates with the severity of neurofibrillary tangle pathology and neurodegeneration in the post-mortem brain. Electronic supplementary material The online version of this article (10.1186/s40478-018-0649-3) contains supplementary material, which is available to authorized users. |
| وصف الملف: | application/pdf |
| تدمد: | 2051-5960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf68c0d2bf4209b6431e41ba2d4b9955Test https://doi.org/10.1186/s40478-018-0649-3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bf68c0d2bf4209b6431e41ba2d4b9955 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20515960 |
|---|