title: Individual estimates of age at detectable amyloid onset for risk factor assessment.
abstract: BACKGROUND
  Individualized estimates of age at detectable amyloid-beta (Aβ) accumulation, distinct from amyloid positivity, allow for analysis of onset age of Aβ accumulation as an outcome measure to understand risk factors.
  
  
  METHODS
  Using longitudinal Pittsburgh compound B (PiB) positron emission tomography data from Baltimore Longitudinal Study of Aging, we estimated the age at which each PiB+ individual began accumulating Aβ. We used survival analysis methods to quantify risk of accumulating Aβ and differences in onset age of Aβ accumulation in relation to APOE ε4 status and sex among 36 APOE ε4 carriers and 83 noncarriers.
  
  
  RESULTS
  Age at onset of Aβ accumulation for the APOE ε4- and ε4+ groups was 73.1 and 60.7, respectively. APOE ε4 positivity conferred a threefold risk of accumulating Aβ after adjusting for sex and education.
  
  
  CONCLUSIONS
  Estimation of onset age of amyloid accumulation may help gauge treatment efficacy in interventions to delay symptom onset in Alzheimer's disease.
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA. Electronic address: murat.bilgel@nih.gov.
authors.forename: Murat
authors.initials: M
authors.lastname: Bilgel
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Prince
authors.affiliation: Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004522:Educational Status; D005260:Female; D006579:Heterozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012307:Risk Factors; D012727:Sex Characteristics; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D019275:Radiopharmaceuticals; D013844:Thiazoles
keywords: APOE; Age at onset; Amyloid imaging; PET; Pittsburgh compound B