| 21. |
- Lleo, A., et al.
(författare)
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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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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
- 2018
-
Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Herschel/HIFI deepens the circumstellar NH3 enigma
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L7-
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Discovery of water vapour in the carbon star V Cygni from observations with Herschel/HIFI
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L5-
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Tidskriftsartikel (refereegranskat)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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| 26. |
- Neufeld, D. A., et al.
(författare)
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The Widespread Occurrence of Water Vapor in the Circumstellar Envelopes of Carbon-Rich Asymptotic Giant Branch Stars: First Results From a Survey With Herschel/HIFI
- 2011
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Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 727:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the preliminary results of a survey for water vapor in a sample of eight C stars with large mid-IR continuum fluxes: V384 Per, CIT 6, V Hya, Y CVn, IRAS 15194-5115, V Cyg, S Cep, and IRC+40540. This survey, performed using the HIFI instrument on board the Herschel Space Observatory, entailed observations of the lowest transitions of both ortho-and para-water: the 556.936 GHz 1(10)-1(01) and 1113.343 GHz 1(11)-0(00) transitions, respectively. Water vapor was unequivocally detected in all eight of the target stars. Prior to this survey, IRC+10216 was the only carbon-rich asymptotic giant branch (AGB) star from which thermal water emissions had been discovered, in that case with the use of the Submillimeter Wave Astronomy Satellite (SWAS). Our results indicate that IRC+10216 is not unusual, except insofar as its proximity to Earth leads to a large line flux that was detectable with SWAS. The water spectral line widths are typically similar to those of CO rotational lines, arguing against the vaporization of a Kuiper Belt analog being the general explanation for water vapor in carbon-rich AGB stars. There is no apparent correlation between the ratio of the integrated water line fluxes to the 6.3 mu m continuum flux-a ratio which measures the water outflow rate-and the total mass-loss rate for the stars in our sample.
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| 27. |
- Schmidt, M. R., et al.
(författare)
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Herschel/HIFI observations of the circumstellar ammonia lines in IRC+10216
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592
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Tidskriftsartikel (refereegranskat)abstract
- Context. A discrepancy exists between the abundance of ammonia (NH3) derived previously for the circumstellar envelope (CSE) of IRC+10216 from far-IR submillimeter rotational lines and that inferred from radio inversion or mid-infrared (MIR) absorption transitions. Aims. To address the discrepancy described above, new high-resolution far-infrared (FIR) observations of both ortho-and para-NH3 transitions toward IRC+10216 were obtained with Herschel, with the goal of determining the ammonia abundance and constraining the distribution of NH3 in the envelope of IRC+10216. Methods. We used the Heterodyne Instrument for the Far Infrared (HIFI) on board Herschel to observe all rotational transitions up to the J = 3 level (three ortho-and six para-NH3 lines). We conducted non-LTE multilevel radiative transfer modelling, including the effects of near-infrared (NIR) radiative pumping through vibrational transitions. The computed emission line profiles are compared with the new HIFI data, the radio inversion transitions, and the MIR absorption lines in the nu(2) band taken from the literature. Results. We found that NIR pumping is of key importance for understanding the excitation of rotational levels of NH3. The derived NH3 abundances relative to molecular hydrogen were (2.8 +/- 0.5) x 10(-8) for ortho-NH3 and (3.2(-0.6)(+0.7)) x 10(-8) for para-NH3, consistent with an ortho/para ratio of 1. These values are in a rough agreement with abundances derived from the inversion transitions, as well as with the total abundance of NH3 inferred from the MIR absorption lines. To explain the observed rotational transitions, ammonia must be formed near to the central star at a radius close to the end of the wind acceleration region, but no larger than about 20 stellar radii (1 sigma confidence level).
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| 28. |
- Teyssier, D., et al.
(författare)
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Herschel/HIFI observations of red supergiants and yellow hypergiants I. Molecular inventory
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. A99 (article no.)-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Red supergiant stars (RSGs) and yellow hypergiant stars (YHGs) are believed to be the high-mass counterparts of stars in the asymptotic giant branch (AGB) and early post-AGB phases. As such, they are scarcer and the properties and evolution of their envelopes are still poorly understood. Aims. We study the mass-loss in the post main-sequence evolution of massive stars, through the properties of their envelopes in the intermediate and warm gas layers. These are the regions where the acceleration of the gas takes place and the most recent mass-loss episodes can be seen. Methods. We used the HIFI instrument on-board the Herschel Space Observatory to observe sub-millimetre and far-infrared (FIR) transitions of CO, water, and their isotopologues in a sample of two RSGs (NML Cyg and Betelgeuse) and two YHGs (IRC + 10420 and AFGL 2343) stars. We present an inventory of the detected lines and analyse the information revealed by their spectral profiles. A comparison of the line intensity and shape in various transitions is used to qualitatively derive a picture of the envelope physical structure. On the basis of the results presented in an earlier study, we model the CO and (CO)-C-13 emission in IRC + 10420 and compare it to a set of lines ranging from the millimetre to the FIR. Results. Red supergiants have stronger high-excitation lines than the YHGs, indicating that they harbour dense and hot inner shells contributing to these transitions. Consequently, these high-J lines in RSGs originate from acceleration layers that have not yet reached the circumstellar terminal velocity and have narrower profiles than their flat-topped lower-J counterparts. The YHGs tend to lack this inner component, in line with the picture of detached, hollow envelopes derived from studies at longer wavelengths. NH3 is only detected in two sources (NML Cyg and IRC + 10420), which are also observed to be the strongest water-line emitters of the studied sample. In contrast, OH is detected in all sources and does not seem to correlate with the water line intensities. We show that the IRC + 10420 model derived solely from millimetre low-J CO transitions is capable of reproducing the high-J transitions when the temperature in the inner shell is simply lowered by about 30%.
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| 29. |
- Varga, A. W., et al.
(författare)
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Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid A beta 42 Levels in Cognitively Normal Elderly
- 2016
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 39:11, s. 2041-2048
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (A beta). We thus aimed to examine relationships between concentrations of A beta 42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. Methods: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF A beta 42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" A beta 42 groups to compare SWS bout length using survival analyses. Results: A significant inverse correlation was found between CSF A beta 42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF A beta 42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF A beta 42. Conclusions: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF A beta 42, suggesting that disturbed sleep might drive an increase in soluble brain A beta levels prior to amyloid deposition.
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| 30. |
- Alcolea, D., et al.
(författare)
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Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias
- 2021
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 92:11, s. 1206-1214
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: All categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer's disease (AD) through an easy and minimally invasive approach. Methods: We measured Aβ, pTau181 and neurofilament light (NfL) in 150 plasma samples of the Sant Pau Initiative on Neurodegeneration cohort including patients with mild cognitive impairment, AD dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal participants. We classified participants in the AT(N) categories according to CSF biomarkers and studied the diagnostic value of plasma biomarkers within each category individually and in combination. Results: The plasma Aβ composite, pTau181 and NfL yielded areas under the curve (AUC) of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective A, T and N categories. The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A-T- participants. There was a moderate correlation between plasma Aβ composite and CSF Aβ1-42/Aβ1-40 (Rho=-0.5, p<0.001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p<0.001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p<0.001). Conclusions: Plasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. A blood AT(N) signature may facilitate early diagnosis and follow-up of patients with AD through an easy and minimally invasive approach. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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