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- 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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| 6. |
- 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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| 7. |
- Abellán, C., et al.
(författare)
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Challenging Local Realism with Human Choices
- 2018
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 557, s. 212-216
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Tidskriftsartikel (refereegranskat)abstract
- A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
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| 9. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 15. |
- Hillier, J. K., et al.
(författare)
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Manual mapping of drumlins in synthetic landscapes to assess operator effectiveness
- 2015
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Ingår i: Journal of Maps. - : Informa UK Limited. - 1744-5647. ; 11:5, s. 719-729
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Tidskriftsartikel (refereegranskat)abstract
- Mapped topographic features are important for understanding processes that sculpt the Earth's surface. This paper presents maps that are the primary product of an exercise that brought together 27 researchers with an interest in landform mapping wherein the efficacy and causes of variation in mapping were tested using novel synthetic DEMs containing drumlins. The variation between interpreters (e.g. mapping philosophy, experience) and across the study region (e.g. woodland prevalence) opens these factors up to assessment. A priori known answers in the synthetics increase the number and strength of conclusions that may be drawn with respect to a traditional comparative study. Initial results suggest that overall detection rates are relatively low (34-40%), but reliability of mapping is higher (72-86%). The maps form a reference dataset.
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- Roberson-Nay, Roxann, et al.
(författare)
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Longitudinal Stability of Genetic and Environmental Influences on Irritability : From Childhood to Young Adulthood
- 2015
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Ingår i: American Journal of Psychiatry. - Arlington, USA : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 172:7, s. 657-664
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Little is known about genetic influences on juvenile irritability and whether such influences are developmentally stable and/or dynamic. This study examined the temporal pattern of genetic and environmental effects on irritability using data from a prospective, four-wave longitudinal twin study.Method: Parents and their twin children (N=2,620 children) from the Swedish Twin Study of Child and Adolescent Development reported on the children's irritability, defined using a previously identified scale from the Child Behavior Checklist.Results: Genetic effects differed across the sexes, with males exhibiting increasing heritability from early childhood through young adulthood and females exhibiting decreasing heritability. Genetic innovation was also more prominent in males than in females, with new genetic risk factors affecting irritability in early and late adolescence for males. Shared environment was not a primary influence on irritability for males or females. Unique, nonshared environmental factors suggested strong effects early for males followed by an attenuating influence, whereas unique environmental factors were relatively stable for females.Conclusions: Genetic effects on irritability are developmentally dynamic from middle childhood through young adulthood, with males and females displaying differing patterns. As males age, genetic influences on irritability increase while nonshared environmental influences weaken. Genetic contributions are quite strong in females early in life but decline in importance with age. In girls, nonshared environmental influences are fairly stable throughout development.
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