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- Coomans, Emma M., et al.
(författare)
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In vivo tau pathology is associated with synaptic loss and altered synaptic function
- 2021
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. Methods: Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [18F]flortaucipir PET, dynamic 60-min [11C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [18F]flortaucipir- and [11C]UCB-J-specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [18F]flortaucipir BPND, [11C]UCB-J BPND and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. Results: Across subjects, higher regional [18F]flortaucipir uptake was associated with lower [11C]UCB-J uptake. Within subjects, the association between [11C]UCB-J and [18F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [18F]flortaucipir and lower [11C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. Conclusions: These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.
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| 2. |
- Santegoets, Saskia J A M, et al.
(författare)
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Transcriptional profiling of human skin-resident Langerhans cells and CD1a+ dermal dendritic cells: differential activation states suggest distinct functions.
- 2008
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Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 84, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- In human skin, two main populations of dendritic cells (DC) can be discriminated: dermal DC (DDC) and epidermal Langerhans cells (LC). Although extensively studied, most of the knowledge about DDC and LC phenotype and function is obtained from studying DDC and LC cultured in vitro or DDC and LC migrated from skin explants. These studies have left the exact relationship between steady-state human LC and DDC unclear: in particular, whether CD1a(+) DDC represent migrated LC or whether they constitute a separate subset. To gain further insight in the kinship between skin-resident CD1a(+) DDC and LC, we analyzed CD1a(+) DDC and LC, isolated from steady-state skin samples, by high-density microarray analysis. Results show that the CD1a(+) DDC specifically express markers associated with DDC phenotype, such as the macrophage mannose receptor, DC-specific ICAM-grabbing nonintegrin, the scavenger receptor CD36, coagulation factor XIIIa, and chemokine receptor CCR5, whereas LC specifically express Langerin, membrane ATPase (CD39), and CCR6, all hallmarks of the LC lineage. In addition, under steady-state conditions, both DC subsets display a strikingly different activation status, indicative of distinct functional properties. CD1a(+) DDC exhibit a more activated, proinflammatory, migratory, and T cell-stimulatory profile, as compared with LC, whereas LC mainly express molecules involved in cell adhesion and DC retention in the epidermis. In conclusion, transcriptional profiling is consistent with the notion that CD1a(+) DDC and LC represent two distinct DC subsets but also that under steady-state conditions, CD1a(+) DDC and epidermal LC represent opposites of the DC activation spectrum.
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