title: Identification of misdiagnosed fronto-temporal dementia using APOE genotype and phenotype-genotype correlation analyses.
abstract: 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), phenotypegenotype 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 ε4 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández
authors.forename: Ana
authors.initials: A
authors.lastname: Mauleón
authors.forename: Maiteé
authors.initials: M
authors.lastname: Rosense-Roca
authors.forename: Montserrat
authors.initials: M
authors.lastname: Alegret
authors.forename: Georgina
authors.initials: G
authors.lastname: Vinyes
authors.forename: Anna
authors.initials: A
authors.lastname: Espinosa
authors.forename: Oscar
authors.initials: O
authors.lastname: Sotolongo-Grau
authors.forename: James T
authors.initials: JT
authors.lastname: Becker
authors.forename: Sergi
authors.initials: S
authors.lastname: Valero
authors.forename: Lluís
authors.initials: L
authors.lastname: Tarraga
authors.forename: Oscar L
authors.initials: OL
authors.lastname: López
authors.forename: Agustín
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Fundacio ACE, Marques de Sentmenat, 57, 08029 Barcelona (Spain). aruiz@fundacioace.com.
authors.forename: Mercè
authors.initials: M
authors.lastname: Boada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D003951:Diagnostic Errors; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D001057:Apolipoproteins E