Using plasma amyloid beta protein (Abeta42) levels as an intermediate, quantitative phenotype for late onset Alzheimer's disease (LOAD), we previously obtained significant linkage at approximately 80 cM on chromosome 10. Linkage to the same region was obtained independently in a study of affected LOAD sib-pairs. Together, these two studies provide strong evidence for a novel LOAD locus on chromosome 10 that acts to increase Abeta42. VR22 is a large (1.7 Mb) gene located at 80 cM that encodes alpha-T catenin, which is a binding partner of beta catenin. This makes VR22 an attractive candidate gene because beta catenin interacts with presenilin 1, which has many mutations that elevate Abeta42 and cause early onset familial AD. We identified two intronic VR22 SNPs (4360 and 4783) in strong linkage disequilibrium (LD) that showed highly significant association (P=0.0001 and 0.0006) with plasma Abeta42 in 10 extended LOAD families. This association clearly contributed to the linkage at approximately 80 cM because the lod scores decreased when linkage analysis was performed conditional upon the VR22 association. This association replicated in another independent set of 12 LOAD families (P=0.04 for 4783 and P=0.08 for 4360). Bounding of the association region using multiple SNPs showed VR22 to be the only confirmed gene within the region of association. These findings indicate that VR22 has variant(s) which influence Abeta42 and contribute to the previously reported linkage for plasma Abeta42 in LOAD families.

This study describes current practice patterns of VTE screening and prophylaxis in high-risk bariatric surgery. Nearly all surgeons agree on risk factors that qualify patients as high risk, but only half routinely screen patients preoperatively. Preoperative VTE chemoprophylaxis is used by nearly all surgeons, but the duration of therapy varies. Use of IVC filters is not routine, and postoperative screening was performed by less than half of the respondents. An understanding of current practice patterns yields insight into the rates of VTE and shows variability in the need for evidence-based prophylaxis and standardized screening.

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