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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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| 3. |
- DeMott, Paul J., et al.
(författare)
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The Fifth International Workshop on Ice Nucleation phase 2 (FIN-02) : Laboratory intercomparison of ice nucleation measurements
- 2018
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 11:11, s. 6231-6257
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Tidskriftsartikel (refereegranskat)abstract
- The second phase of the Fifth International Ice Nucleation Workshop (FIN-02) involved the gathering of a large number of researchers at the Karlsruhe Institute of Technology's Aerosol Interactions and Dynamics of the Atmosphere (AIDA) facility to promote characterization and understanding of ice nucleation measurements made by a variety of methods used worldwide. Compared to the previous workshop in 2007, participation was doubled, reflecting a vibrant research area. Experimental methods involved sampling of aerosol particles by direct processing ice nucleation measuring systems from the same volume of air in separate experiments using different ice nucleating particle (INP) types, and collections of aerosol particle samples onto filters or into liquid for sharing amongst measurement techniques that post-process these samples. In this manner, any errors introduced by differences in generation methods when samples are shared across laboratories were mitigated. Furthermore, as much as possible, aerosol particle size distribution was controlled so that the size limitations of different methods were minimized. The results presented here use data from the workshop to assess the comparability of immersion freezing measurement methods activating INPs in bulk suspensions, methods that activate INPs in condensation and/or immersion freezing modes as single particles on a substrate, continuous flow diffusion chambers (CFDCs) directly sampling and processing particles well above water saturation to maximize immersion and subsequent freezing of aerosol particles, and expansion cloud chamber simulations in which liquid cloud droplets were first activated on aerosol particles prior to freezing. The AIDA expansion chamber measurements are expected to be the closest representation to INP activation in atmospheric cloud parcels in these comparisons, due to exposing particles freely to adiabatic cooling. The different particle types used as INPs included the minerals illite NX and potassium feldspar (K-feldspar), two natural soil dusts representative of arable sandy loam (Argentina) and highly erodible sandy dryland (Tunisia) soils, respectively, and a bacterial INP (Snomax®). Considered together, the agreement among post-processed immersion freezing measurements of the numbers and fractions of particles active at different temperatures following bulk collection of particles into liquid was excellent, with possible temperature uncertainties inferred to be a key factor in determining INP uncertainties. Collection onto filters for rinsing versus directly into liquid in impingers made little difference. For methods that activated collected single particles on a substrate at a controlled humidity at or above water saturation, agreement with immersion freezing methods was good in most cases, but was biased low in a few others for reasons that have not been resolved, but could relate to water vapor competition effects. Amongst CFDC-style instruments, various factors requiring (variable) higher supersaturations to achieve equivalent immersion freezing activation dominate the uncertainty between these measurements, and for comparison with bulk immersion freezing methods. When operated above water saturation to include assessment of immersion freezing, CFDC measurements often measured at or above the upper bound of immersion freezing device measurements, but often underestimated INP concentration in comparison to an immersion freezing method that first activates all particles into liquid droplets prior to cooling (the PIMCA-PINC device, or Portable Immersion Mode Cooling chAmber-Portable Ice Nucleation Chamber), and typically slightly underestimated INP number concentrations in comparison to cloud parcel expansions in the AIDA chamber; this can be largely mitigated when it is possible to raise the relative humidity to sufficiently high values in the CFDCs, although this is not always possible operationally. Correspondence of measurements of INPs among direct sampling and post-processing systems varied depending on the INP type. Agreement was best for Snomax® particles in the temperature regime colder than -10°C, where their ice nucleation activity is nearly maximized and changes very little with temperature. At temperatures warmer than -10°C, Snomax® INP measurements (all via freezing of suspensions) demonstrated discrepancies consistent with previous reports of the instability of its protein aggregates that appear to make it less suitable as a calibration INP at these temperatures. For Argentinian soil dust particles, there was excellent agreement across all measurement methods; measures ranged within 1 order of magnitude for INP number concentrations, active fractions and calculated active site densities over a 25 to 30°C range and 5 to 8 orders of corresponding magnitude change in number concentrations. This was also the case for all temperatures warmer than -25°C in Tunisian dust experiments. In contrast, discrepancies in measurements of INP concentrations or active site densities that exceeded 2 orders of magnitude across a broad range of temperature measurements found at temperatures warmer than -25°C in a previous study were replicated for illite NX. Discrepancies also exceeded 2 orders of magnitude at temperatures of -20 to -25°C for potassium feldspar (K-feldspar), but these coincided with the range of temperatures at which INP concentrations increase rapidly at approximately an order of magnitude per 2°C cooling for K-feldspar. These few discrepancies did not outweigh the overall positive outcomes of the workshop activity, nor the future utility of this data set or future similar efforts for resolving remaining measurement issues. Measurements of the same materials were repeatable over the time of the workshop and demonstrated strong consistency with prior studies, as reflected by agreement of data broadly with parameterizations of different specific or general (e.g., soil dust) aerosol types. The divergent measurements of the INP activity of illite NX by direct versus post-processing methods were not repeated for other particle types, and the Snomax° data demonstrated that, at least for a biological INP type, there is no expected measurement bias between bulk collection and direct immediately processed freezing methods to as warm as -10°C. Since particle size ranges were limited for this workshop, it can be expected that for atmospheric populations of INPs, measurement discrepancies will appear due to the different capabilities of methods for sampling the full aerosol size distribution, or due to limitations on achieving sufficient water supersaturations to fully capture immersion freezing in direct processing instruments. Overall, this workshop presents an improved picture of present capabilities for measuring INPs than in past workshops, and provides direction toward addressing remaining measurement issues.
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| 5. |
- Aranha, M. R., et al.
(författare)
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Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome
- 2023
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 19:11, s. 4817-4827
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBasal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. MethodsWe included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. ResultsIn DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. DiscussionBF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS.
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| 6. |
- Bartels-Rausch, Thorsten, et al.
(författare)
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Ice structures, patterns, and processes: A view across the icefields
- 2012
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Ingår i: Reviews of Modern Physics. ; 84:2, s. 885-944
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Forskningsöversikt (refereegranskat)abstract
- From the frontiers of research on ice dynamics in its broadest sense, this review surveys the structures of ice, the patterns or morphologies it may assume, and the physical and chemical processes in which it is involved. Open questions in the various fields of ice research in nature are highlighted, ranging from terrestrial and oceanic ice on Earth, to ice in the atmosphere, to ice on other Solar System bodies and in interstellar space.
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| 9. |
- Habes, M., et al.
(författare)
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Disentangling Heterogeneity in Alzheimer's Disease and Related Dementias Using Data-Driven Methods
- 2020
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223. ; 88:1, s. 70-82
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Tidskriftsartikel (refereegranskat)abstract
- Brain aging is a complex process that includes atrophy, vascular injury, and a variety of age-associated neurodegenerative pathologies, together determining an individual's course of cognitive decline. While Alzheimer's disease and related dementias contribute to the heterogeneity of brain aging, these conditions themselves are also heterogeneous in their clinical presentation, progression, and pattern of neural injury. We reviewed studies that leveraged data-driven approaches to examining heterogeneity in Alzheimer's disease and related dementias, with a principal focus on neuroimaging studies exploring subtypes of regional neurodegeneration patterns. Over the past decade, the steadily increasing wealth of clinical, neuroimaging, and molecular biomarker information collected within large-scale observational cohort studies has allowed for a richer understanding of the variability of disease expression within the aging and Alzheimer's disease and related dementias continuum. Moreover, the availability of these large-scale datasets has supported the development and increasing application of clustering techniques for studying disease heterogeneity in a data-driven manner. In particular, data-driven studies have led to new discoveries of previously unappreciated disease subtypes characterized by distinct neuroimaging patterns of regional neurodegeneration, which are paralleled by heterogeneous profiles of pathological, clinical, and molecular biomarker characteristics. Incorporating these findings into novel frameworks for more differentiated disease stratification holds great promise for improving individualized diagnosis and prognosis of expected clinical progression, and provides opportunities for development of precision medicine approaches for therapeutic intervention. We conclude with an account of the principal challenges associated with datadriven heterogeneity analyses and outline avenues for future developments in the field.
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| 10. |
- Ozden, C., et al.
(författare)
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FDG Uptake in the Basal Forebrain as Measured by Digital High-Resolution PET Is a Promising Marker of Basal Forebrain Degeneration in the Lewy Body Disease Spectrum A Pilot Study
- 2020
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Ingår i: Clinical Nuclear Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0363-9762 .- 1536-0229. ; 45:4, s. 261-266
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Cognitive decline in diseases of the Lewy body spectrum (LBS) is linked to dysfunction/degeneration of the basal forebrain (BF). Assessment of glucose metabolism in the BF by FDG PET is hampered by the small size of the BF and limited spatial resolution of conventional PET. This pilot study tested the feasibility of assessing BF glucose metabolism by high-resolution digital PET (dPET). Patients and Methods The retrospective study included 12 LBS patients (61-86 years, 5 demented). Whole-brain stereotactic normalization to anatomical standard space was followed by local stereotactic normalization of a 7 x 7 x 7-cm(3) box around the BF to a custom-made 1 x 1 x 1-mm(3) FDG dPET template. FDG uptake was scaled voxelwise to mean FDG uptake in the pons. Scaled FDG uptake in the BF was compared between demented and nondemented LBS patients and tested for correlation with cortical FDG uptake. Results Scaled FDG uptake in the BF was significantly lower in demented compared with nondemented patients (1.14 +/- 0.09 vs 1.25 +/- 0.06, P = 0.031). Brain-wide voxel-based testing for correlations with scaled FDG uptake in the BF revealed a large cluster comprising medial and ventrolateral frontal cortex, anterior cingulate cortex, insular cortex, and striatum as well as smaller clusters in motor cortex and occipital cortex (P < 0.001, uncorrected). Conclusions These results suggest that dementia-associated BF degeneration in LBS can be sensitively measured as reduced BF FDG uptake on dPET. More accurate delineation of the BF based on individual high-resolution MRI might be useful to make optimal use of improved spatial resolution of dPET and to correct for possible disease- and age-dependent partial volume effects.
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