| 1. |
- Ashton, Nicholas J., et al.
(författare)
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An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders.
- 2020
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Ingår i: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 16, s. 265-284
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Forskningsöversikt (refereegranskat)abstract
- Cerebrospinal fluid analyses and neuroimaging can identify the underlying pathophysiology at the earliest stage of some neurodegenerative disorders, but do not have the scalability needed for population screening. Therefore, a blood-based marker for such pathophysiology would have greater utility in a primary care setting and in eligibility screening for clinical trials. Rapid advances in ultra-sensitive assays have enabled the levels of pathological proteins to be measured in blood samples, but research has been predominantly focused on Alzheimer disease (AD). Nonetheless, proteins that were identified as potential blood-based biomarkers for AD, for example, amyloid-β, tau, phosphorylated tau and neurofilament light chain, are likely to be relevant to other neurodegenerative disorders that involve similar pathological processes and could also be useful for the differential diagnosis of clinical symptoms. This Review outlines the neuropathological, clinical, molecular imaging and cerebrospinal fluid features of the most common neurodegenerative disorders outside the AD continuum and gives an overview of the current status of blood-based biomarkers for these disorders.
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| 2. |
- Ashton, Nicholas J., et al.
(författare)
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Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration
- 2019
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Eggens, Veerle Rc, et al.
(författare)
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EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations.
- 2014
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Ingår i: Orphanet journal of rare diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Pontocerebellar hypoplasia (PCH) represents a group of neurodegenerative disorders with prenatal onset. Eight subtypes have been described thus far (PCH1-8) based on clinical and genetic features. Common characteristics include hypoplasia and atrophy of the cerebellum, variable pontine atrophy, and severe mental and motor impairments. PCH1 is distinctly characterized by the combination with degeneration of spinal motor neurons. Recently, mutations in the exosome component 3 gene (EXOSC3) have been identified in approximately half of the patients with PCH subtype 1.
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| 4. |
- Wilhelmsson, Ulrika, 1970, et al.
(författare)
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Injury leads to the appearance of cells with characteristics of both microglia and astrocytes in mouse and human brain.
- 2017
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Ingår i: Cerebral cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 27:6, s. 3360-3377
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Tidskriftsartikel (refereegranskat)abstract
- Microglia and astrocytes have been considered until now as cells with very distinct identities. Here, we assessed the heterogeneity within microglia/monocyte cell population in mouse hippocampus and determined their response to injury, by using single-cell gene expression profiling of cells isolated from uninjured and deafferented hippocampus. We found that in individual cells, microglial markers Cx3cr1, Aif1, Itgam, and Cd68 were co-expressed. Interestingly, injury led to the co-expression of the astrocyte marker Gfap in a subpopulation of Cx3cr1-expressing cells from both the injured and contralesional hippocampus. Cells co-expressing astrocyte and microglia markers were also detected in the in vitro LPS activation/injury model and in sections from human brain affected by stroke, Alzheimer's disease, and Lewy body dementia. Our findings indicate that injury and chronic neurodegeneration lead to the appearance of cells that share molecular characteristics of both microglia and astrocytes, 2 cell types with distinct embryologic origin and function.
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