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

Methyl chavicol: characterization of its biogenic emission rate

We report measurements of ambient atmospheric mixing ratios for methyl chavicol and determine its biogenic emission rate. Methyl chavicol, a biogenic oxygenated aromatic compound, is abundant within and above Blodgett Forest, a ponderosa pine forest in the Sierra Nevada Mountains of California. Methyl chavicol was detected simultaneously by three in-situ instruments – a gas chromatograph with mass spectrometer detector (GC-MS), a proton transfer reaction mass spectrometer (PTR-MS), and a thermal desorption aerosol GC-MS (TAG) – and found to be abundant within and above Blodgett Forest. Methyl chavicol atmospheric mixing ratios are strongly correlated with 2-methyl-3-buten- 2-ol (MBO), a light- and temperature-dependent biogenic emission from the ponderosa pine trees at Blodgett Forest. Scaling from this correlation, methyl chavicol emissions account for 4–68% of the carbon mass emitted as MBO in the daytime, depending on the season. From this relationship, we estimate a daytime basal emission rate of 0.72– 10.2μgCg−1 h−1, depending on needle age and seasonality. We also present the first observations of its oxidation products (4-methoxybenzaldehyde and 4-methyoxy benzene acetaldehyde) in the ambient atmosphere. Methyl chavicol is a major essential oil component of many plant species. This work suggests that methyl chavicol plays a significant role in the atmospheric chemistry of Blodgett Forest, and potentially other sites, and should be included explicitly in both biogenic volatile organic carbon emission and atmospheric chemistry models

General ability measurement: An application of multidimensional item response theory

computerized adaptive testing, general cognitive ability, general mental ability, multidimensional adaptive testing, multidimensional item response theory, personnel selection, tests,