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

Ion energies in an open-diode hollow cathode discharge

Ion energy measurements from a ¼ inch cathode were made with krypton and xenon expellants at a range of flow rates and discharge currents using an electrostatic energy analyzer mounted on axis. High energy ion content scaled strongly with discharge current and inversely with mass flow rate and molecular mass suggesting a possible MDH production mechanism. At high current conditions for krypton and xenon peak ion energies exceeded 130eV (>17kms-1) and 75eV (>10kms-1) with high energy tails extending well beyond 140eV and 200eV respectively. No conclusive correlation was found with discharge noise in the form of high frequency voltage oscillations and high energy ion conten