title: Mapping the effects of ApoE4, age and cognitive status on 18F-florbetapir PET measured regional cortical patterns of beta-amyloid density and growth.
abstract: BACKGROUND
  Although it is well known that many clinical and genetic factors have been associated with beta-amyloid deposition, few studies have examined the interactions of such factors across different stages of Alzheimer's pathogenesis.
  
  
  METHODS
  We used 18F-florbetapir F18 PET imaging to quantify neuritic beta-amyloid plaque density across four cortical regions in 602 elderly (55-94 years) subjects from the national ADNI biomarker study. The group comprised of 194 normal elderly, 212 early mild cognitive impairment [EMCI], 132 late mild cognitive impairment [LMCI], and 64 mild Alzheimer's (AD).
  
  
  RESULTS
  In a model incorporating multiple predictive factors, the effect of apolipoprotein E ε4 and diagnosis was significant on all four cortical regions. The highest signals were seen in cingulate followed by frontal and parietal with lowest signals in temporal lobe (p<0.0001). The effect of apolipoprotein E ε4 (Cohen's D 0.96) on beta-amyloid plaque density was approximately twice as large as the effect of a diagnosis of AD (Cohen's D 0.51) and thrice as large as the effect of a diagnosis of LMCI (Cohen's D 0.34) (p<0.0001). Surprisingly, ApoE ε4+ normal controls had greater mean plaque density across all cortical regions than ε4- EMCI and ε4- LMCI (p<0.0001, p=0.0009) and showed higher, though non-significant, mean value than ε4- AD patients (p<0.27). ApoE ε4+ EMCI and LMCI subjects had significantly greater mean plaque density across all cortical regions than ε4- AD patients (p<0.027, p<0.0001).
  
  
  CONCLUSIONS
  Neuritic amyloid plaque load across progressive clinical stages of AD varies strongly by ApoE4 genotype. These findings support the need for better pathology-based and supported diagnosis in routine practice. Our data also provides additional evidence for a temporal offset between amyloid deposition and clinically relevant symptoms.
authors.affiliation: Department of Psychiatry, Duke University Health System, Duke University Medical Center, Durham, NC, USA.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Murphy
authors.forename: Susan M
authors.initials: SM
authors.lastname: Landau
authors.forename: Kingshuk Roy
authors.initials: KR
authors.lastname: Choudhury
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hostage
authors.forename: Katie S
authors.initials: KS
authors.lastname: Shpanskaya
authors.forename: Haris I
authors.initials: HI
authors.lastname: Sair
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Petrella
authors.forename: Terence Z
authors.initials: TZ
authors.lastname: Wong
authors.forename: P Murali
authors.initials: PM
authors.lastname: Doraiswamy
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000682:Amyloid / Q000235:genetics / Q000378:metabolism; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000473:pathology; D005026:Ethylene Glycols; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000235:genetics* / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D000682:Amyloid; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D005026:Ethylene Glycols; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C545186:florbetapir