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

Magnetic Phase Diagram for the Spinel Ferrite Series MgFe2-xCrxO4 and Mg1-xZnxFel.5Cr0.5O4 as Determined by Mössbauer Spectroscopy

The spinel series MgFe2-xCrxO4 (0.0≤x≤2.0) (MFC) and Mg1-xZnxFel.5Cr0.5O4 (0.0≤x≤1.0) (MZFC) are progressively diluted on the A-sites by non-magnetic Mg2+ and/or Zn2+ ions as x increases. The different magnetic states as a function of temperature and composition could be determined by Mössbauer spectroscopy in conjunction with high external magnetic fields. From the spectra it was derived that only for the spinel samples MFC with x≤0.6 and MZFC with ≤0.1 a pure ferrimagnetic behavior exists down to 4K. In the composition range 0.8≤x≤1.2 for MFC and 0.2≤x≤0.7 for MZFC a marked canting of the A- and B-site spins was observed below a characteristic temperature Tf indicating a re-entrant semi-spinglass behavior. Finally, for the samples with x>1.2 (ZFC) and x>0.7 (MZFC) an incomplete alignment of the spins remained up to the paramagnetic transition temperature Tg pointing to pure semi-spin glasses. Together with the temperature dependence of the average magnetic hyperfine field the complete magnetic phase diagram could be derived

Fe57 MÖSSBAUER SPECTROSCOPY ON TITANIUM-RICH IRON TITANATES Fe3-xTixO4 (x = 1., 0.95, 0.9)

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