| 1. |
- de Rojas, I., et al.
(author)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
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| 3. |
- Bellenguez, C, et al.
(author)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Journal article (peer-reviewed)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- van der Lee, S. J., et al.
(author)
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A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
- 2019
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 237-250
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Journal article (peer-reviewed)abstract
- The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC gamma 2 pathway as drug-target.
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| 8. |
- Bujarrabal, V., et al.
(author)
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Herschel/HIFI observations of high-J CO transitions in the protoplanetary nebula CRL 618
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L3-
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Journal article (peer-reviewed)abstract
- Aims. We aim to study the physical conditions, particularly the excitation state, of the intermediate-temperature gas components in the protoplanetary nebula CRL 618. These components are particularly important for understanding the evolution of the nebula. Methods. We performed Herschel/HIFI observations of several CO lines in the far-infrared/sub-mm in the protoplanetary nebula CRL 618. The high spectral resolution provided by HIFI allows measurement of the line profiles. Since the dynamics and structure of the nebula is well known from mm-wave interferometric maps, it is possible to identify the contributions of the different nebular components (fast bipolar outflows, double shells, compact slow shell) to the line profiles. The observation of these relatively high-energy transitions allows an accurate study of the excitation conditions in these components, particularly in the warm ones, which cannot be properly studied from the low-energy lines. Results. The (CO)-C-12 J = 16-15, 10-9, and 6-5 lines are easily detected in this source. Both (CO)-C-13 J = 10-9 and 6-5 are also detected. Wide profiles showing spectacular line wings have been found, particularly in (CO)-C-12 J = 16-15. Other lines observed simultaneously with CO are also shown. Our analysis of the CO high-J transitions, when compared with the existing models, confirms the very low expansion velocity of the central, dense component, which probably indicates that the shells ejected during the last AGB phases were driven by radiation pressure under a regime of maximum transfer of momentum. No contribution of the diffuse halo found from mm-wave data is identified in our spectra, because of its low temperature. We find that the fast bipolar outflow is quite hot, much hotter than previously estimated; for instance, gas flowing at 100 km s(-1) must have a temperature higher than similar to 200 K. Probably, this very fast outflow, with a kinematic age
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| 9. |
- Decin, L., et al.
(author)
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Water content and wind acceleration in the envelope around the oxygen-rich AGB star IK Tauri as seen by Herschel/HIFI
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L4-
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Journal article (peer-reviewed)abstract
- During their asymptotic giant branch evolution, low-mass stars lose a significant fraction of their mass through an intense wind, enriching the interstellar medium with products of nucleosynthesis. We observed the nearby oxygen-rich asymptotic giant branch star IK Tau using the high-resolution HIFI spectrometer onboard Herschel. We report on the first detection of (H2O)-O-16 and the rarer isotopologues (H2O)-O-17 and (H2O)-O-18 in both the ortho and para states. We deduce a total water content (relative to molecular hydrogen) of 6.6 x 10(-5), and an ortho-to-para ratio of 3:1. These results are consistent with the formation of H2O in thermodynamical chemical equilibrium at photospheric temperatures, and does not require pulsationally induced non-equilibrium chemistry, vaporization of icy bodies or grain surface reactions. High-excitation lines of (CO)-C-12, (CO)-C-13, (SiO)-Si-28, (SiO)-Si-29, (SiO)-Si-30, HCN, and SO have also been detected. From the observed line widths, the acceleration region in the inner wind zone can be characterized, and we show that the wind acceleration is slower than hitherto anticipated.
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| 10. |
- Alcolea, J., et al.
(author)
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HIFISTARS Herschel/HIFI observations of VY Canis Majoris. Molecular-line inventory of the envelope around the largest known star
- 2013
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 559, s. (article nr.) A93-
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Journal article (peer-reviewed)abstract
- Aims.The study of the molecular gas in the circumstellar envelopes of evolved stars is normally undertaken by observing lines ofCO (and other species) in the millimetre-wave domain. In general, the excitation requirements of the observed lines are low at thesewavelengths, and therefore these observations predominantly probe the cold outer envelope while studying the warm inner regions ofthe envelopes normally requires sub-millimetre (sub-mm) and far-infrared (FIR) observational data.Methods.To gain insight into the physical conditions and kinematics of the warm (100–1000 K) gas around the red hyper-giantVY CMa, we performed sensitive high spectral resolution observations of molecular lines in the sub-mm/FIR using the HIFI instru-ment of theHerschelSpace Observatory. We observed CO, H2O, and other molecular species, sampling excitation energies from afew tens to a few thousand K. These observations are part of theHerschelguaranteed time key program HIFISTARS.Results.We detected theJ=6–5,J=10–9, andJ=16–15 lines of12CO and13CO at∼100, 300, and 750 K above the groundstate (and the13COJ=9–8 line). These lines are crucial for improving the modelling of the internal layers of the envelope aroundVY CMa. We also detected 27 lines of H2O and its isotopomers, and 96 lines of species such as NH3,SiO,SO,SO2HCN, OH andothers, some of them originating from vibrationally excited levels. Three lines were not unambiguously assigned.Conclusions.Our observations confirm that VY CMa’s envelope must consist of two or more detached components. The molecularexcitation in the outer layers is significantly lower than in the inner ones, resulting in strong self-absorbed profiles in molecular linesthat are optically thick in this outer envelope, for instance, low-lying lines of H2O. Except for the most abundant species, CO and H2O,most of the molecular emission detected at these sub-mm/FIR wavelengths arise from the central parts of the envelope. The spectrumof VY CMa is very prominent in vibrationally excited lines, which are caused by the strong IR pumping present in the central regions.Compared with envelopes of other massive evolved stars, VY CMa’s emission is particularly strong in these vibrationally excitedlines, as well as in the emission from less abundant species such as H13CN, SO, and NH3.
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| 11. |
- Bujarrabal, V., et al.
(author)
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Herschel/HIFI observations of molecular emission in protoplanetary nebulae and young planetary nebulae
- 2012
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537, s. Article Number: A8-
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Journal article (peer-reviewed)abstract
- Aims. We aim to study the physical conditions, particularly the excitation state, of the intermediate-temperature gas in protoplanetary nebulae and young planetary nebulae (PPNe, PNe). The information that the observations of the different components deliver is of particular importance for understanding the evolution of these objects. Methods. We performed Herschel/HIFI observations of intermediate-excitation molecular lines in the far-infrared/submillimeter range in a sample of ten nebulae. The high spectral resolution provided by HIFI allows the accurate measurement of the line profiles. The dynamics and evolution of these nebulae are known to result from the presence of several gas components, notably fast bipolar outflows and slow shells (that often are the fossil AGB shells), and the interaction between them. Because of the diverse kinematic properties of the different components, their emissions can be identified in the line profiles. The observation of these high-energy transitions allows an accurate study of the excitation conditions, particularly in the warm gas, which cannot be properly studied from the low-energy lines. Results. We have detected FIR/sub-mm lines of several molecules, in particular of (CO)-C-12, (CO)-C-13, and H2O. Emission from other species, like NH3, OH, (H2O)-O-18, HCN, SiO, etc., has been also detected. Wide profiles showing sometimes spectacular line wings have been found. We have mainly studied the excitation properties of the high-velocity emission, which is known to come from fast bipolar outflows. From comparison with general theoretical predictions, we find that CRL 618 shows a particularly warm fast wind, with characteristic kinetic temperature T-k greater than or similar to 200 K. In contrast, the fast winds in OH 231.8+4.2 and NGC 6302 are cold, T-k similar to 30 K. Other nebulae, like CRL 2688, show intermediate temperatures, with characteristic values around 100 K. We also discuss how the complex structure of the nebulae can affect our estimates, considering two-component models. We argue that the differences in temperature in the different nebulae can be caused by cooling after the gas acceleration (that is probably caused by shocks); for instance, CRL 618 is a case of very recent acceleration, less than similar to 100 yr ago, while the fast gas in OH 231.8+4.2 was accelerated similar to 1000 yr ago. We also find indications that the densest gas tends to be cooler, which may be explained by the expected increase of the radiative cooling efficiency with the density.
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| 12. |
- Gonzalez, Maria Camila, et al.
(author)
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Cognitive and motor decline in dementia with lewy bodies and Parkinson's disease dementia
- 2023
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In: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:6, s. 980-986
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Journal article (peer-reviewed)abstract
- Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD).Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts.Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157).Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]).Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.
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| 13. |
- Harwit, M., et al.
(author)
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Polarisation observations of VY Canis Majoris H2O 5(32)-4(41) 620.701 GHz maser emission with HIFI
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L51-
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Journal article (peer-reviewed)abstract
- Context. Water vapour maser emission from evolved oxygen-rich stars remains poorly understood. Additional observations, including polarisation studies and simultaneous observation of different maser transitions may ultimately lead to greater insight. Aims. We have aimed to elucidate the nature and structure of the VY CMa water vapour masers in part by observationally testing a theoretical prediction of the relative strengths of the 620.701 GHz and the 22.235 GHz maser components of ortho H2O. Methods. In its high-resolution mode (HRS) the Herschel Heterodyne Instrument for the Far Infrared (HIFI) offers a frequency resolution of 0.125 MHz, corresponding to a line-of-sight velocity of 0.06 km s(-1), which we employed to obtain the strength and linear polarisation of maser spikes in the spectrum of VY CMa at 620.701 GHz. Simultaneous ground based observations of the 22.235 GHz maser with the Max-Planck-Institut fur Radioastronomie 100-m telescope at Effelsberg, provided a ratio of 620.701 GHz to 22.235 GHz emission. Results. We report the first astronomical detection to date of H2O maser emission at 620.701 GHz. In VY CMa both the 620.701 and the 22.235 GHz polarisation are weak. At 620.701 GHz the maser peaks are superposed on what appears to be a broad emission component, jointly ejected from the star. We observed the 620.701 GHz emission at two epochs 21 days apart, both to measure the potential direction of linearly polarised maser components and to obtain a measure of the longevity of these components. Although we do not detect significant polarisation levels in the core of the line, they rise up to approximately 6% in its wings.
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| 14. |
- Hong, S. J., et al.
(author)
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TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels
- 2021
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:10, s. 1628-1640
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Journal article (peer-reviewed)abstract
- Introduction Neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are biomarkers for Alzheimer's disease (AD) to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. Methods We performed genome-wide association studies (GWAS) using DNA and cerebrospinal fluid (CSF) samples from the EMIF-AD Multimodal Biomarker Discovery study for discovery, and the Alzheimer's Disease Neuroimaging Initiative study for validation analyses. GWAS were performed for all three CSF biomarkers using linear regression models adjusting for relevant covariates. Results We identify novel genome-wide significant associations between DNA variants in TMEM106B and CSF levels of NfL, and between CPOX and YKL-40. We confirm previous work suggesting that YKL-40 levels are associated with DNA variants in CHI3L1. Discussion Our study provides important new insights into the genetic architecture underlying interindividual variation in three AD-related CSF biomarkers. In particular, our data shed light on the sequence of events regarding the initiation and progression of neuropathological processes relevant in AD.
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| 15. |
- Jansen, Willemijn J, et al.
(author)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Journal article (peer-reviewed)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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| 16. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Journal article (peer-reviewed)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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| 17. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Journal article (peer-reviewed)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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| 18. |
- Justtanont, Kay, 1965, et al.
(author)
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A HIFI preview of warm molecular gas around chi Cygni: first detection of H2O emission toward an S-type AGB star
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L6-
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Journal article (peer-reviewed)abstract
- Aims. A set of new, sensitive, and spectrally resolved, sub-millimeter line observations are used to probe the warm circumstellar gas around the S-type AGB star chi Cyg. The observed lines involve high rotational quantum numbers, which, combined with previously obtained lower-frequency data, make it posible to study in detail the chemical and physical properties of, essentially, the entire circumstellar envelope of chi Cyg. Methods. The data were obtained using the HIFI instrument aboard Herschel, whose high spectral resolution provides valuable information about the line profiles. Detailed, non-LTE, radiative transfer modelling, including dust radiative transfer coupled with a dynamical model, has been performed to derive the temperature, density, and velocity structure of the circumstellar envelope. Results. We report the first detection of circumstellar H2O rotational emission lines in an S-star. Using the high-J CO lines to derive the parameters for the circumstellar envelope, we modelled both the ortho-and para-H2O lines. Our modelling results are consistent with the velocity structure expected for a dust-driven wind. The derived total H2O abundance (relative to H-2) is (1.1 +/- 0.2) x 10(-5), much lower than that in O-rich stars. The derived ortho-to-para ratio of 2.1 +/- 0.6 is close to the high-temperature equilibrium limit, consistent with H2O being formed in the photosphere.
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| 19. |
- Justtanont, Kay, 1965, et al.
(author)
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Herschel/HIFI observations of O-rich AGB stars: molecular inventory
- 2012
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537, s. Article Number: A144 -
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Journal article (peer-reviewed)abstract
- Aims. Spectra, taken with the heterodyne instrument, HIFI, aboard the Herschel Space Observatory, of O-rich asymptotic giant branch (AGB) stars which form part of the guaranteed time key program HIFISTARS are presented. The aim of this program is to study the dynamical structure, mass-loss driving mechanism, and chemistry of the outflows from AGB stars as a function of chemical composition and initial mass. Methods. We used the HIFI instrument to observe nine AGB stars, mainly in the H2O and high rotational CO lines. We investigate the correlation between line luminosity, line ratio and mass-loss rate, line width and excitation energy. Results. A total of nine different molecules, along with some of their isotopologues have been identified, covering a wide range of excitation temperature. Maser emission is detected in both the ortho-and para-H2O molecules. The line luminosities of ground state lines of ortho- and para-H2O, the high-J CO and NH3 lines show a clear correlation with mass-loss rate. The line ratios of H2O and NH3 relative to CO J = 6-5 correlate with the mass-loss rate while ratios of higher CO lines to the 6-5 is independent of it. In most cases, the expansion velocity derived from the observed line width of highly excited transitions formed relatively close to the stellar photosphere is lower than that of lower excitation transitions, formed farther out, pointing to an accelerated outflow. In some objects, the vibrationally excited H2O and SiO which probe the acceleration zone suggests the wind reaches its terminal velocity already in the innermost part of the envelope, i.e., the acceleration is rapid. Interestingly, for R Dor we find indications of a deceleration of the outflow in the region where the material has already escaped from the star.
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| 20. |
- Kruse, N., et al.
(author)
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Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study
- 2015
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 36:9, s. 2587-2596
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Journal article (peer-reviewed)abstract
- Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program -Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given. (C) 2015 Elsevier Inc. All rights reserved.
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| 21. |
- Lleo, A., et al.
(author)
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Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer's disease in adults with Down syndrome
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer's disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73-0.87] and 0.92 [95% CI 0.89-0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS. Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer's disease (AD) pathology. Here, the authors investigated whether plasma ptau181 could be a potential biomarker of AD in individuals with Down syndrome (DS) and find plasma p-tau181 can detect AD in DS adults.
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| 22. |
- Mattsson, Niklas, et al.
(author)
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Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
- 2018
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In: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Journal article (peer-reviewed)abstract
- Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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| 23. |
- Mattsson, Niklas, et al.
(author)
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Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
- 2018
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In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Journal article (peer-reviewed)abstract
- Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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| 24. |
- Menten, K. M., et al.
(author)
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Herschel/HIFI deepens the circumstellar NH3 enigma
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L7-
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Journal article (peer-reviewed)abstract
- Context. Circumstellar envelopes (CSEs) of a variety of evolved stars have been found to contain ammonia (NH3) in amounts that exceed predictions from conventional chemical models by many orders of magnitude. Aims. The observations reported here were performed in order to better constrain the NH3 abundance in the CSEs of four, quite diverse, oxygen-rich stars using the NH3 ortho J(K) = 1(0)-0(0) ground-state line. Methods. We used the Heterodyne Instrument for the Far Infrared aboard Herschel to observe the NH3 J(K) = 1(0)-0(0) transition near 572.5 GHz, simultaneously with the ortho-H2O J(Ka,Kc) = 1(1,0)-1(0,1) transition, toward VY CMa, OH 26.5+0.6, IRC+10420, and IK Tau. We conducted non-LTE radiative transfer modeling with the goal to derive the NH3 abundance in these objects' CSEs. For the last two stars, Very Large Array imaging of NH3 radio-wavelength inversion lines were used to provide further constraints, particularly on the spatial extent of the NH3-emitting regions. Results. We find remarkably strong NH3 emission in all of our objects with the NH3 line intensities rivaling those of the ground state H2O line. The NH3 abundances relative to H-2 are very high and range from 2 x 10(-7) to 3 x 10(-6) for the objects we have studied. Conclusions. Our observations confirm and even deepen the circumstellar NH3 enigma. While our radiative transfer modeling does not yield satisfactory fits to the observed line profiles, it does lead to abundance estimates that confirm the very high values found in earlier studies. New ways to tackle this mystery will include further Herschel observations of more NH3 lines and imaging with the Expanded Very Large Array.
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| 25. |
- Neufeld, D. A., et al.
(author)
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Discovery of water vapour in the carbon star V Cygni from observations with Herschel/HIFI
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L5-
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Journal article (peer-reviewed)abstract
- We report the discovery of water vapour toward the carbon star V Cygni. We have used Herschel's HIFI instrument, in dual beam switch mode, to observe the 1(11)-0(00) para-water transition at 1113.3430 GHz in the upper sideband of the Band 4b receiver. The observed spectral line profile is nearly parabolic, but with a slight asymmetry associated with blueshifted absorption, and the integrated antenna temperature is 1.69 +/- 0.17 K km s(-1). This detection of thermal water vapour emission, carried out as part of a small survey of water in carbon-rich stars, is only the second such detection toward a carbon-rich AGB star, the first having been obtained by the Submillimeter Wave Astronomy Satellite toward IRC+ 10216. For an assumed ortho-to-para ratio of 3 for water, the observed line intensity implies a water outflow rate similar to 3-6 x 10(-5) Earth masses per year and a water abundance relative to H-2 of similar to 2-5 x 10(-6). This value is a factor of at least 10(4) larger than the expected photospheric abundance in a carbon-rich environment, and - as in IRC+ 10216 - raises the intriguing possibility that the observed water is produced by the vapourisation of orbiting comets or dwarf planets. However, observations of the single line observed to date do not permit us to place strong constraints upon the spatial distribution or origin of the observed water, but future observations of additional transitions will allow us to determine the inner radius of the H2O-emitting zone, and the H2O ortho-to-para ratio, and thereby to place important constraints upon the origin of the observed water emission.
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