| 1. |
- Vogel, Jacob W., et al.
(författare)
-
Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
-
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.
|
|
| 2. |
- Zhou, XP, et al.
(författare)
-
Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
-
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.
|
|
| 3. |
- Aguer, P, et al.
(författare)
-
Skin morphology and layer identification using different STIM geometries
- 2005
-
Ingår i: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 231:1-4, s. 292-299
-
Tidskriftsartikel (refereegranskat)abstract
- The use of on-axis geometry in scanning transmission ion microscopy (STIM) has been widely used for thin biological sample structure identification. In this configuration, the lateral resolution is optimised so that micron or submicron beam spots are easily achieved even for classic microbeam lines. Off-axis STIM was more particularly employed for rapid imaging, and also (when associated to a scattering set-up) for normalising elemental contents obtained by other ion beam analysis techniques in organic thin samples. Due to the very small beam current required, on-axis STIM is a stand-alone technique. Off-axis STIM can be advantageous as it enables the simultaneous utilisation of PIXE and RBS techniques. In this paper, the STIM images obtained with an on-axis geometry, a standard off-axis geometry and a recently developed on-off geometry are presented and discussed. Data from skin samples are used for comparison purposes aiming at studying skin permeability to sunscreens. Skin is a stratified tissue and the precise identification of skin layers is needed to ascertain the penetration depth of the physical filter from the formulation. In addition to the intrinsic difference in image quality due to the beam resolution, the influence of the detector type, implanted silicon detector versus Si pin diode, is discussed on the basis of their energy resolution.. their resistance to beam damage as well as the effect
|
|
| 4. |
|
|
| 5. |
- Lekki, J., et al.
(författare)
-
On the follicular pathway of percutaneous uptake of nanoparticles: Ion microscopy and autoradiography studies
- 2007
-
Ingår i: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 260:1, s. 174-177
-
Tidskriftsartikel (refereegranskat)abstract
- We report on the visualization of the penetration of sunscreen formulations containing TiO2 nanoparticles (about 20 nm primary particle size) into hair follicles of both human and porcine skin using the complementary methods of ion microscopy (PIXE, RBS, STIM) and autoradiography. Particles were found as deep as approx. 400 pin in the follicle, obviously introduced mechanically rather than by a diffusive process. No particles were observed in vital tissue nor in sebaceous glands. (c) 2007 Elsevier B.V. All rights reserved.
|
|
