21 research outputs found
Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered
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Cosmological constraints from the tomography of DES-Y3 galaxies with CMB lensing from ACT DR4
Abstract
We present a measurement of the cross-correlation between the MagLim galaxies selected from the Dark Energy Survey (DES) first three years of observations (Y3) and cosmic microwave background (CMB) lensing from the Atacama Cosmology Telescope (ACT) Data Release 4 (DR4), reconstructed over ∼ 436 deg2 of the sky. Our galaxy sample, which covers ∼ 4143 deg2, is divided into six redshift bins spanning the redshift range of 0.20<z<1.05. We adopt a blinding procedure until passing all consistency and systematics tests. After imposing scale cuts for the cross-power spectrum measurement, we reject the null hypothesis of no correlation at 9.1σ. We constrain cosmological parameters from a joint analysis of galaxy and CMB lensing-galaxy power spectra considering a flat ΛCDM model, marginalized over 23 astrophysical and systematic nuisance parameters. We find the clustering amplitude S
8 ≡ σ
8(Ω
m
/0.3)0.5Â =Â 0.75+0.04
-0.05. In addition, we constrain the linear growth of cosmic structure as a function of redshift. Our results are consistent with recent DES Y3 analyses and suggest a preference for a lower S
8 compared to results from measurements of CMB anisotropies by the Planck satellite, although at a mild level (< 2σ) of statistical significance. </jats:p