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- 2017
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Journal article (peer-reviewed)
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| 2. |
- 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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| 3. |
- Marconi, A., et al.
(author)
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ANDES, the high resolution spectrograph for the ELT : science case, baseline design and path to construction
- 2022
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
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Conference paper (peer-reviewed)abstract
- The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs (UBV, RIZ, YJH) providing a spectral resolution of similar to 100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 mu m with the goal of extending it to 0.35-2.4 mu m with the addition of a K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Its modularity will ensure that ANDES can be placed entirely on the ELT Nasmyth platform, if enough mass and volume is available, or partly in the Coude room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of more than 200 scientists and engineers which represent the majority of the scientific and technical expertise in the field among ESO member states.
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| 4. |
- Petroff, E., et al.
(author)
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A polarized fast radio burst at low Galactic latitude
- 2017
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In: Monthly notices of the Royal Astronomical Society. - : Oxford Academic. - 0035-8711 .- 1365-2966. ; 469:4, s. 4465-4482
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Journal article (peer-reviewed)abstract
- We report on the discovery of a new fast radio burst (FRB), FRB 150215, with the Parkes radio telescope on 2015 February 15. The burst was detected in real time with a dispersion measure (DM) of 1105.6 +/- 0.8 pc cm(-3), a pulse duration of 2.8(-0.5)(+1.2) ms, and a measured peak flux density assuming that the burst was at beam centre of 0.7(-0.1)(+0.2) Jy. The FRB originated at a Galactic longitude and latitude of 24.66 degrees, 5.28 degrees and 25 degrees away from the Galactic Center. The burst was found to be 43 +/- 5 per cent linearly polarized with a rotation measure (RM) in the range -9 < RM < 12 rad m(-2) (95 per cent confidence level), consistent with zero. The burst was followed up with 11 telescopes to search for radio, optical, X-ray, gamma-ray and neutrino emission. Neither transient nor variable emission was found to be associated with the burst and no repeat pulses have been observed in 17.25 h of observing. The sightline to the burst is close to the Galactic plane and the observed physical properties of FRB 150215 demonstrate the existence of sight lines of anomalously low RM for a given electron column density. The Galactic RM foreground may approach a null value due to magnetic field reversals along the line of sight, a decreased total electron column density from the Milky Way, or some combination of these effects. A lower Galactic DM contribution might explain why this burst was detectable whereas previous searches at low latitude have had lower detection rates than those out of the plane.
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| 8. |
- Duffau, S., et al.
(author)
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The Gaia-ESO Survey : Galactic evolution of sulphur and zinc
- 2017
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 604
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Journal article (peer-reviewed)abstract
- Context. Due to their volatile nature, when sulphur and zinc are observed in external galaxies, their determined abundances represent the gas-phase abundances in the interstellar medium. This implies that they can be used as tracers of the chemical enrichment of matter in the Universe at high redshift. Comparable observations in stars are more difficult and, until recently, plagued by small number statistics. Aims. We wish to exploit the Gaia-ESO Survey (GES) data to study the behaviour of sulphur and zinc abundances of a large number of Galactic stars, in a homogeneous way. Methods. By using the UVES spectra of the GES sample, we are able to assemble a sample of 1301 Galactic stars, including stars in open and globular clusters in which both sulphur and zinc were measured. Results. We confirm the results from the literature that sulphur behaves as an α-element. We find a large scatter in [Zn/Fe] ratios among giant stars around solar metallicity. The lower ratios are observed in giant stars at Galactocentric distances less than 7.5 kpc. No such effect is observed among dwarf stars, since they do not extend to that radius. Conclusions. Given the sample selection, giants and dwarfs are observed at different Galactic locations, and it is plausible, and compatible with simple calculations, that Zn-poor giants trace a younger population more polluted by SN Ia yields. It is necessary to extend observations in order to observe both giants and dwarfs at the same Galactic location. Further theoretical work on the evolution of zinc is also necessary.
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| 9. |
- Gaetani, L., et al.
(author)
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Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis
- 2019
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In: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:9, s. 2157-2163
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Journal article (peer-reviewed)abstract
- Background Cognitive impairment (CI) is a disabling symptom of multiple sclerosis (MS). Axonal damage disrupts neural circuits and may play a role in determining CI, but its detection and monitoring are not routinely performed. Cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a promising marker of axonal damage in MS. Objective To retrospectively examine the relationship between CSF NfL and CI in MS patients. Methods CSF NfL concentration was measured in 28 consecutive newly diagnosed MS patients who underwent a neuropsychological evaluation with the Brief Repeatable Battery of Neuropsychological tests (BRBN). Results CSF NfL was higher in patients with overall CI (947.8 +/- 400.7 vs 518.4 +/- 424.7 pg/mL, p < 0.01), and with impairment in information processing speed (IPS) (820.8 +/- 413.6 vs 513.6 +/- 461.4 pg/mL, p < 0.05) and verbal fluency (1292 +/- 511 vs 582.8 +/- 395.4 pg/mL, p < 0.05), and it positively correlated with the number of impaired BRBN tests (r = 0.48, p = 0.01) and cognitive domains (r = 0.47, p = 0.01). Multivariate analyses taking into account potential confounders confirmed these findings. Conclusion CSF NfL is higher in MS patients with CI and impaired IPS and verbal fluency. Large myelinated axons injury, causing neural disconnection, may be an important determinant of CI in MS and can be reliably measured through CSF NfL.
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| 10. |
- Saddiki, H., et al.
(author)
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Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study
- 2020
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In: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:8
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Journal article (peer-reviewed)abstract
- Background The epsilon 4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association betweenAPOEgenotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of beta-amyloid peptide (A, beta-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated withAPOEgenotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least oneAPOE epsilon 4 allele. Compared with non-epsilon 4 carriers, heterozygous epsilon 4 carriers had a 4.6 (95% confidence interval 4.1-5.2;p< 0.001) and epsilon 4/epsilon 4 homozygotes a 25.4 (20.4-31.2;p< 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (pfor interaction < 0.001). The PAF associated with carrying at least one epsilon 4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect ofAPOE epsilon 2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE epsilon 4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect ofAPOE epsilon 4 at the population level. Author summaryWhy was this study done? The epsilon 4 allele of apolipoprotein E () gene () and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The recent development of diagnostic criteria based on biomarkers that reflect brain beta-amyloid and tau lesions (beta-amyloid deposition, pathologic tau, neurodegeneration [A/T/N] classification]) increases homogeneity in diagnosed cases. The strength of association of AD with risk factors can be better determined using biomarker-based AD compared with AD diagnosis based only on clinical criteria because the latter are known to lack specificity as a result of difficulties in ruling out other causes of dementia. What did the researchers do and find? We compared the overall and age-specific association between and AD using a case-control study that included 1,593 AD cases from memory clinics with positive cerebrospinal fluid biomarkers and 11,723 dementia-free controls drawn from two longitudinal cohort studies. The use of a large number of cases and controls allows assessment of whether the association between and AD is dependent on age. Compared with controls, patients with AD were more likely to carry one (odds ratio [OR] = 4.6) or two (OR = 25.3). This association was significantly modified by age, with the strongest association seen between 65 and 70 years of age and weaker associations at the two tails of the age distribution. What do these findings mean? Incorporating biomarkers for diagnosis of AD identified an association with that is apparently greater than has been previously reported using clinical diagnosis of the disease. The impact of on the risk of AD was strongest between the 65 and 70 years of age, earlier than the mean age at diagnosis in this study, which was 72.8 years.
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| 11. |
- van Doorn, Ljcv, et al.
(author)
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Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes
- 2017
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 56:2, s. 543-555
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.
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