New insights into the genetic etiology of Alzheimer's disease and related dementias

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

New insights into the genetic etiology of Alzheimer’s disease and related dementias

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. © 2022, The Author(s)

Measurement of single-diffractive dijet production in proton–proton collisions at √s=8Te with the CMS and TOTEM experiments

Measurements are presented of the single-diffractive dijet cross section and the diffractive cross section as a function of the proton fractional momentum loss ξ and the four-momentum transfer squared t. Both processes pp→pX and pp→Xp, i.e. with the proton scattering to either side of the interaction point, are measured, where X includes at least two jets; the results of the two processes are averaged. The analyses are based on data collected simultaneously with the CMS and TOTEM detectors at the LHC in proton–proton collisions at s=8Te during a dedicated run with β∗=90m at low instantaneous luminosity and correspond to an integrated luminosity of 37.5nb-1. The single-diffractive dijet cross section σjjpX, in the kinematic region ξ< 0.1 , 0.03<|t|<1Ge2, with at least two jets with transverse momentum pT>40Ge, and pseudorapidity | η| < 4.4 , is 21.7±0.9(stat)-3.3+3.0(syst)±0.9(lumi)nb. The ratio of the single-diffractive to inclusive dijet yields, normalised per unit of ξ, is presented as a function of x, the longitudinal momentum fraction of the proton carried by the struck parton. The ratio in the kinematic region defined above, for x values in the range - 2.9 ≤ log 10x≤ - 1.6 , is R=(σjjpX/Δξ)/σjj=0.025±0.001(stat)±0.003(syst), where σjjpX and σjj are the single-diffractive and inclusive dijet cross sections, respectively. The results are compared with predictions from models of diffractive and nondiffractive interactions. Monte Carlo predictions based on the HERA diffractive parton distribution functions agree well with the data when corrected for the effect of soft rescattering between the spectator partons. © 2020, CERN for the benefit of the CMS and TOTEM collaborations

Erratum to: Measurement of exclusive Υ photoproduction from protons in pPb collisions at s NN = 5.02 TeV (The European Physical Journal C, (2019), 79, 3, (277), 10.1140/epjc/s10052-019-6774-8)

In this article the author name Luigi Calligaris was incorrectly written as A. Calligaris. The original article has been corrected. © CERN for the benefit of the CMS collaboration 2022