| 1. |
- Vogel, Jacob W., et al.
(författare)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 2. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 8. |
- Cumnock, J. A., et al.
(författare)
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Interplanetary magnetic field control of theta aurora development
- 2002
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Ingår i: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202. ; 107:A7
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Tidskriftsartikel (refereegranskat)abstract
- [1] We ascertain the influence of the B-y component of the interplanetary magnetic field (IMF) on theta aurora evolution. During most cases where a transpolar arc is observed to move across the polar region, and form a theta aurora, there are brief (minutes) southward excursions of IMF B-z, however northward IMF is required prior to theta aurora formation. Observations show that theta aurora can form during strictly northward IMF with its motion consistent with a change in sign of IMF B-y. It is important to note that since transpolar arcs can persist for 20-30 min after the IMF turns southward, errors will occur in assigning instantaneous IMF conditions to snapshots'' of particular auroral patterns. We consider the entire evolution of the theta aurora and the changing IMF conditions. The influence of IMF B-y is best illustrated by examples which occur during steady northward IMF as compared to times when the IMF is northward on average. We show examples, provided by the Polar UV imager, when the IMF is steady northward. For one case, DMSP F13 and F14 provide in situ measurements of precipitating particles, ionospheric plasma flows and ion density. This unique data set enables us to analyze in detail the evolution of a theta aurora, in one case crossing the entire polar region. No sign change in B-z is needed for theta aurora formation.
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| 10. |
- Germany, G A, et al.
(författare)
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Remote determination of auroral energy characteristics during substorm activity
- 1997
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 24, s. 995-998
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Tidskriftsartikel (refereegranskat)abstract
- Ultraviolet auroral images from the Ultraviolet Imager (UVI) onboard the POLAR satellite can be used as quantitative remote diagnostics of the auroral regions, yielding estimates of incident energy characteristics, compositional changes, and other higher order data products. Here incident energy estimates derived from UVI are compared with in situ measurements of the same parameters from an overflight by the DMSP F12 satellite coincident with the UVI image times during substorm activity occurring on May 19, 1996. This event was simultaneously observed by WIND, GEOTAIL, INTERBALL, DMSP and NOAA spacecraft as well as by POLAR.
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| 11. |
- Cumnock, Judy, et al.
(författare)
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POLAR UVI Observations of Auroral Oval Intensifications During a Transpolar Arc Event on December 7, 1996
- 2000
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The evolution of the northern hemisphere aurora is examined during a time when the IMF makes three brief southward excursions after a change in the sign of By during an extended period of northward IMF. POLAR UVI provides images of the aurora while DMSP F13 and F14 provide in situ measurements of precipitating particles, ionospheric plasma flows and ion density. Three different intensifications located in the nightside auroral oval occur during northward turnings of the IMF after brief periods of southward IMF. Spatial expansion, intensity of emissions and their duration are related to the length of time the IMF is southward prior to the northward turning. Thus the longer the period of enhanced magnetospheric convection the more intense the ionospheric response. Observations of a transpolar arc indicate that when the transpolar arc reaches highest latitudes it is located on a spatially narrow region of closed field lines, which extends along the noon-midnight meridian. UV observations indicate a connection between the transpolar arc and the nightside auroral enhancements. Precipitating particles associated with both features are attributed to a plasma sheet boundary layer source in the magnetotail implying a magnetospheric connection between the transpolar arc and the nightside auroral oval intensification.
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| 12. |
- Oishi, Yumiko, et al.
(författare)
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SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism
- 2017
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Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 25:2, s. 412-427
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages play pivotal roles in both the induction and resolution phases of inflammatory processes. Macrophages have been shown to synthesize anti-inflammatory fatty acids in an LXR-dependent manner, but whether the production of these species contributes to the resolution phase of inflammatory responses has not been established. Here, we identify a biphasic program of gene expression that drives production of anti-inflammatory fatty acids 12-24 hr following TLR4 activation and contributes to downregulation of mRNAs encoding pro-inflammatory mediators. Unexpectedly, rather than requiring LXRs, this late program of anti-inflammatory fatty acid biosynthesis is dependent on SREBP1 and results in the uncoupling of NFκB binding from gene activation. In contrast to previously identified roles of SREBP1 in promoting production of IL1β during the induction phase of inflammation, these studies provide evidence that SREBP1 also contributes to the resolution phase of TLR4-induced gene activation by reprogramming macrophage lipid metabolism.
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