| 1. |
- Jansen, Willemijn J, et al.
(författare)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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| 2. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 3. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 4. |
- Hellwig, Johannes, et al.
(författare)
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Measuring elasticity of wet cellulose beads with an AFM colloidal probe using a linearized DMT model
- 2017
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Ingår i: Analytical Methods. - : Royal Society of Chemistry. - 1759-9660 .- 1759-9679. ; 9:27, s. 4019-4022
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Tidskriftsartikel (refereegranskat)abstract
- The mechanical properties of wet cellulose are investigated using an atomic force microscope AFM and calculated using a linearized DMT model. Measurements were performed using a model system of gel beads made of cellulose with different charge densities, which show a high impact on the mechanical properties of the cellulose in wet state.
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| 5. |
- Hellwig, Johannes, et al.
(författare)
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Measuring elasticity of wet cellulose fibres with AFM using indentation and a linearized Hertz model
- 2018
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Ingår i: Analytical Methods. - : Royal Society of Chemistry. - 1759-9660 .- 1759-9679. ; 10:31
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Tidskriftsartikel (refereegranskat)abstract
- The mechanical properties of different pulp fibres in liquid were measured using an atomic force microscope. Specifically a custom-made sample holder was used to indent the fibre surface, without causing any motion, and the Young's modulus was calculated from the indentation using a linearized Hertz model.
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| 6. |
- Hellwig, Raphael, et al.
(författare)
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Ho-Mediated Alkyne Reactions at Low Temperatures on Ag(111)
- 2018
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Ingår i: Chemistry - A European Journal. - : WILEY-V C H VERLAG GMBH. - 0947-6539 .- 1521-3765. ; 24:60, s. 16126-16135
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Tidskriftsartikel (refereegranskat)abstract
- Low-temperature approaches to catalytic conversions promise efficiency, selectivity, and sustainable processes. Control over certain coupling reactions can be obtained via the pre-positioning of reactive moieties by self-assembly. However, in the striving field of on-surface synthesis atomistic precision and control remains largely elusive, because the employed coupling reactions proceed at temperatures beyond the thermal stability of the supramolecular templates. Here, utilizing scanning tunneling microscopy, we demonstrate terminal alkyne on-surface reactions mediated by Ho atoms at a weakly reactive Ag(111) substrate at lowtemperatures. Density functional theory calculations confirm the catalytic activity of the involved adatoms. Pre-deposited Ho induces alkyne dehydrogenation starting at substrate temperatures as low as 100 K. Ho arriving at molecularly pre-covered surfaces held at 130 and 200 K produces covalent enyne-linked dimers and initiates cyclotrimerization, respectively. Statistical product analysis indicates a two-step pathway for the latter, whereby the enyne intermediates influence the distribution of the products. High chemoselectivity results from the absence of cyclotetramerization and diyne-forming homocoupling. Our analysis indicates that mainly the arriving Ho adatoms enable the coupling. These findings support the concept of dynamic heterogeneity by single-atom catalysts and pave the way for alternative means to control on-surface reactions.
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| 7. |
- Herrera, A., et al.
(författare)
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From macroscopic mechanics to cell-effective stiffness within highly aligned macroporous collagen scaffolds
- 2019
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Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems. - : ELSEVIER. - 0928-4931 .- 1873-0191. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- In the design of macroporous biomaterial scaffolds, attention is payed predominantly to the readily accessible macroscopic mechanical properties rather than to the mechanical properties experienced by the cells adhering to the material. However, the direct cell mechanical environment has been shown to be of special relevance for biological processes such as proliferation, differentiation and extracellular matrix formation both in vitro and in vivo. In this study we investigated how individual architectural features of highly aligned macroporous collagen scaffolds contribute to its mechanical properties on the macroscopic vs. the microscopic scale. Scaffolds were produced by controlled freezing and freeze-drying, a method frequently used for manufacturing of macroporous biomaterials. The individual architectural features of the biomaterial were carefully characterized to develop a finite element model (FE-model) that finally provided insights in the relation between the biomaterial's mechanical properties on the macro-scale and the properties on the micro-scale, as experienced by adhering cells. FE-models were validated by experimental characterization of the scaffolds, both on the macroscopic and the microscopic level, using mechanical compression testing and atomic force microscopy. As a result, a so-called cell-effective stiffness of these non-trivial scaffold architectures could be predicted for the first time. A linear dependency between the macroscopic scaffold stiffness and the cell-effective stiffness was found, with the latter being consistently higher by a factor of 6.4 +/- 0.6. The relevance of the cell-effective stiffness in controlling progenitor cell differentiation was confirmed in vitro. The obtained information about the cell-effective stiffness is of particular relevance for the early stages of tissue regeneration, when the cells first populate and interact with the biomaterial. Beyond the specific biomaterial investigated here, the introduced method is transferable to other complex biomaterial architectures. Design-optimization in 3D macroporous scaffolds that are based on a deeper understanding of the mechanical environment provided to the cells will help to enhance biomaterial-based tissue regeneration approaches.
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| 8. |
- Karlsson, Rose-Marie Pernilla, et al.
(författare)
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Carbohydrate gel beads as model probes for quantifying non-ionic and ionic contributions behind the swelling of delignified plant fibers
- 2018
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Ingår i: Journal of Colloid and Interface Science. - : Academic Press. - 0021-9797 .- 1095-7103. ; 519, s. 119-129
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Tidskriftsartikel (refereegranskat)abstract
- Macroscopic beads of water-based gels consisting of uncharged and partially charged beta-(1,4)-D-glucan polymers were developed to be used as a novel model material for studying the water induced swelling of the delignified plant fiber walls. The gel beads were prepared by drop-wise precipitation of solutions of dissolving grade fibers carboxymethylated to different degrees. The internal structure was analyzed using Solid State Cross-Polarization Magic Angle Spinning Carbon-13 Nuclear Magnetic Resonance and Small Angle X-ray Scattering showing that the internal structure could be considered a homogeneous, non-crystalline and molecularly dispersed polymer network. When beads with different charge densities were equilibrated with aqueous solutions of different ionic strengths and/or pH, the change in water uptake followed the trends expected for weak polyelectrolyte gels and the trends found for cellulose-rich fibers. When dried and subsequently immersed in water the beads also showed an irreversible loss of swelling depending on the charge and type of counter-ion which is commonly also found for cellulose-rich fibers. Taken all these results together it is clear that the model cellulose-based beads constitute an excellent tool for studying the fundamentals of swelling of cellulose rich plant fibers, aiding in the elucidation of the different molecular and supramolecular contributions to the swelling.
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| 9. |
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| 10. |
- López Durán, Veronica, 1987-, et al.
(författare)
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Effect of Chemical Functionality on the Mechanical and Barrier Performance of Nanocellulose Films
- 2018
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Ingår i: ACS APPLIED NANO MATERIALS. - : AMER CHEMICAL SOC. - 2574-0970. ; 1:4, s. 1959-1967
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Tidskriftsartikel (refereegranskat)abstract
- In the present work, we have partially modified fibrils chemically to eate a shell of derivatized cellulose that surrounds the crystalline re of native cellulose. Through the different modifications, we aimed creating a toolbox to enable the properties of CNF materials and terials containing CNFs to be tuned to meet specific material demands. total, nine different chemical modifications using different ueous-based procedures were used as chemical pretreatments before CNF oduction through homogenization. Eight of these modifications included riodate oxidation with an average of 27% of the anhydroglucose units the cellulose chain being cleaved into dialdehydes. The presence of dehydes then facilitated a conversion to other functional groups.
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