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- Vogel, Jacob W., et al.
(author)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Journal article (peer-reviewed)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.
(author)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Journal article (peer-reviewed)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.
(author)
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Interplanetary magnetic field control of theta aurora development
- 2002
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In: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202. ; 107:A7
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Journal article (peer-reviewed)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.
(author)
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Remote determination of auroral energy characteristics during substorm activity
- 1997
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 24, s. 995-998
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Journal article (peer-reviewed)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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