期刊
CURRENT ALZHEIMER RESEARCH
卷 11, 期 2, 页码 182-191出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567205010666131212120443
关键词
Alzheimer's disease; apolipoprotein E4; diagnostic classification; frontotemporal lobe dementia; genetics
资金
- Ministerio de Sanidad, Servicios Sociales e Igualdad. Spain [FIS/EC11-358, FIS/P: 10-00945, AATM/390-6-2009]
- Generalitat de Catalunya (Catalan Government) NIA/NIH [AG05133]
Objective: Postmortem and genetic studies of clinically diagnosed Frontotemporal dementia (FTD) patients suggest that a number of clinically diagnosed FTD patients are actually frontal variants of Alzheimer's disease (fvAD). The purpose of this study was to evaluate this hypothesis by combining neuropathological data, genetic association studies of APOE, phenotype-APOE genotype correlations and discriminant analysis techniques. Methods: Neuropathological information on 24 FTD cases, genetic association studies of APOE (168 FTD, 3083 controls and 2528 AD), phenotype-genotype correlations and discriminant techniques (LDA, logistic regression and decision trees) were combined to identify fvAD patients within a clinical FTD series. Results: Four of 24 FTLD patients (16.6%) met criteria for definite AD. By comparing allele and genotype frequencies of APOE in controls, FTD and AD groups and by applying the Hardy-Weinberg equilibrium law (HWE), we inferred a consistent (17.2%) degree of AD contamination in clinical FTD. A penetrance analysis for APOE epsilon 4 genotype in the FTD series identified 14 features for discrimination analysis. These features were compared between clinical AD (n=332) and clinical FTD series (n=168) and classifiers were constructed usinglinear discriminant analysis logistic regression or decision tree techniques. The classifier had 92.8% sensitivity to FTD and 93.4% sensitivity to AD relative to neuropathology (global AUC=0.939, p << 0.001). We identified 30 potential fvAD cases (17.85%) in the clinical FTD sample. Conclusion: The APOE locus association in clinical FTD might be entirely explained by the existence of hidden fvAD cases within an FTD sample. The degree of fvAD contamination can be inferred from APOE genotypes.
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