title: Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD.
abstract: OBJECTIVE
  To investigate association of genetic risk factors for late-onset Alzheimer disease (LOAD) with risk of posterior cortical atrophy (PCA), a syndrome of visual impairment with predominant Alzheimer disease (AD) pathology in posterior cortical regions, and with risk of "posterior AD" neuropathology.
  
  
  METHODS
  We assessed 81 participants with PCA diagnosed clinically and 54 with neuropathologic diagnosis of posterior AD vs 2,523 controls for association with 11 significant single nucleotide polymorphisms (SNPs) from published LOAD risk genome-wide association studies.
  
  
  RESULTS
  There was highly significant association with APOE ε4 and increased risk of PCA (p = 0.0003, odds ratio [OR] = 3.17) and posterior AD (p = 1.11 × 10(-17), OR = 6.43). No other locus was significant after corrections for multiple testing, although rs11136000 near CLU (p = 0.019, OR = 0.60) and rs744373 near BIN1 (p = 0.025, OR = 1. 63) associated nominally significantly with posterior AD, and rs3851179 at the PICALM locus had significant association with PCA (p = 0.0003, OR = 2.84). ABCA7 locus SNP rs3764650, which was also tested under the recessive model because of Hardy-Weinberg disequilibrium, also had nominally significant association with PCA risk. The direction of association at APOE, CLU, and BIN1 loci was the same for participants with PCA and posterior AD. The effects for all SNPs, except rs3851179, were consistent with those for LOAD risk.
  
  
  CONCLUSIONS
  We identified a significant effect for APOE and nominate CLU, BIN1, and ABCA7 as additional risk loci for PCA and posterior AD. Our findings suggest that at least some of the genetic risk factors for LOAD are shared with these atypical conditions and provide effect-size estimates for their future genetic studies.
authors.affiliation: From the Departments of Neuroscience (M.M.C., M.E.M., S.K., T.N., L.M., G.B., S.G.Y., D.W.D., N.E.-T.) and Neurology (Q.u.A.K., N.R.G.-R., N.E.-T.), Mayo Clinic Florida, Jacksonville; and Departments of Biostatistics (J.A., V.S.P.) and Neurology (R.C.P., B.F.B.), Mayo Clinic Minnesota, Rochester.
authors.forename: Minerva M
authors.initials: MM
authors.lastname: Carrasquillo
authors.forename: Qurat ul Ain
authors.initials: Qu
authors.lastname: Khan
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Murray
authors.forename: Siddharth
authors.initials: S
authors.lastname: Krishnan
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Aakre
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Thuy
authors.initials: T
authors.lastname: Nguyen
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Gina
authors.initials: G
authors.lastname: Bisceglio
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Steven G
authors.initials: SG
authors.lastname: Younkin
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Nilüfer
authors.initials: N
authors.lastname: Ertekin-Taner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D001284:Atrophy; D002540:Cerebral Cortex / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D013548:Sweden; D014057:Tomography, X-Ray Computed