APOE is a correlate of phenotypic heterogeneity in Alzheimer disease in a national cohort.

OBJECTIVE: To compare the proportion of APOE ε4 genotype carriers in aphasic vs amnestic variants of Alzheimer disease (AD). METHOD: The proportion of APOE ε4 carriers was compared among the following 3 groups: (1) 42 patients with primary progressive aphasia (PPA) and AD pathology (PPA/AD) enrolled in the Northwestern Alzheimer Disease Center Clinical Core; (2) 1,418 patients with autopsy-confirmed AD and amnestic dementia of the Alzheimer type (DAT/AD); and (3) 2,608 cognitively normal controls (NC). The latter 2 groups were compiled from the National Alzheimer Coordinating Center database. Logistic regression models analyzed the relationship between groups and APOE ε4 carrier status, adjusting for age at onset and sex as needed. RESULTS: Using NC as the reference and adjusting for sex and age, the DAT/AD group was 3.97 times more likely to be APOE ε4 carriers. Adjusting for sex and age at symptom onset, the DAT/AD group was 2.46 times as likely to be carriers compared to PPA/AD. There was no significant difference in the proportion of APOE ε4 carriers for PPA/AD compared to NC. PPA subtypes included 24 logopenic, 10 agrammatic nonfluent, and 8 either mixed (n = 5) or too severe (n = 3) to subtype. The proportion of carriers and noncarriers was similar for logopenic and agrammatic subtypes, both having fewer carriers. CONCLUSION: The proportion of APOE ε4 carriers was elevated in amnestic but not aphasic manifestations of AD. These results suggest that APOE ε4 is an anatomically selective risk factor that preferentially increases the vulnerability to AD pathology of memory-related medial temporal areas rather than language-related neocortices.

Version 3 of the National Alzheimer's Coordinating Center's Uniform Data Set.

INTRODUCTION: In 2015, the US Alzheimer's Disease Centers (ADC) implemented Version 3 of the Uniform Data Set (UDS). This paper describes the history of Version 3 development and the UDS data that are freely available to researchers. METHODS: UDS Version 3 was developed after years of coordination between the National Institute on Aging-appointed Clinical Task Force (CTF), clinicians from ∼30 ADCs, and the National Alzheimer's Coordinating Center (NACC). The CTF recognized the need for updates to align with the state of the science in dementia research, while being flexible to the diverse needs and diseases studied at the ADCs. Version 3 also developed a nonproprietary neuropsychological battery. RESULTS: This paper focuses on the substantial Version 3 changes to the UDS forms related to clinical diagnosis and characterization of clinical symptoms to match updated consensus-based diagnostic criteria. Between March 2015 and March 2018, 4820 participants were enrolled using UDS Version 3. Longitudinal data were available for 25,337 of the 37,568 total participants using all UDS versions. DISCUSSION: The results from utilization of the UDS highlight the possibility for numerous research institutions to successfully collaborate, produce, and use standardized data collection instruments for over a decade.

Quality control, analysis and secure sharing of Luminex® immunoassay data using the open source LabKey Server platform.

BACKGROUND: Immunoassays that employ multiplexed bead arrays produce high information content per sample. Such assays are now frequently used to evaluate humoral responses in clinical trials. Integrated software is needed for the analysis, quality control, and secure sharing of the high volume of data produced by such multiplexed assays. Software that facilitates data exchange and provides flexibility to perform customized analyses (including multiple curve fits and visualizations of assay performance over time) could increase scientists' capacity to use these immunoassays to evaluate human clinical trials. RESULTS: The HIV Vaccine Trials Network and the Statistical Center for HIV/AIDS Research and Prevention collaborated with LabKey Software to enhance the open source LabKey Server platform to facilitate workflows for multiplexed bead assays. This system now supports the management, analysis, quality control, and secure sharing of data from multiplexed immunoassays that leverage Luminex xMAP® technology. These assays may be custom or kit-based. Newly added features enable labs to: (i) import run data from spreadsheets output by Bio-Plex Manager™ software; (ii) customize data processing, curve fits, and algorithms through scripts written in common languages, such as R; (iii) select script-defined calculation options through a graphical user interface; (iv) collect custom metadata for each titration, analyte, run and batch of runs; (v) calculate dose-response curves for titrations; (vi) interpolate unknown concentrations from curves for titrated standards; (vii) flag run data for exclusion from analysis; (viii) track quality control metrics across runs using Levey-Jennings plots; and (ix) automatically flag outliers based on expected values. Existing system features allow researchers to analyze, integrate, visualize, export and securely share their data, as well as to construct custom user interfaces and workflows. CONCLUSIONS: Unlike other tools tailored for Luminex immunoassays, LabKey Server allows labs to customize their Luminex analyses using scripting while still presenting users with a single, graphical interface for processing and analyzing data. The LabKey Server system also stands out among Luminex tools for enabling smooth, secure transfer of data, quality control information, and analyses between collaborators. LabKey Server and its Luminex features are freely available as open source software at http://www.labkey.com under the Apache 2.0 license.