title: Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts.
abstract: Apolipoprotein E (APOE) genotype influences onset age of Alzheimer's disease but effects on disease progression are less clear. We investigated amyloid-β (Aβ) levels and change in relationship to APOE genotype, using 2 different measures of Aβ in 2 different longitudinal cohorts. Aβ accumulation was measured using positron emission tomography (PET) imaging and (11)C-Pittsburgh compound-B (PiB) in 113 Baltimore Longitudinal Study of Aging participants (mean age 77.3 years; 107 normal, 6 cognitively impaired) and cerebral spinal fluid (CSF) Aβ1-42 assays in 207 BIOCARD study participants (mean age 62 years; 195 normal, 12 cognitively impaired). Participants in both cohorts had up to 7 serial assessments (mean 2.3-2.4). PET-PiB retention increased and CSF Aβ1-42 declined longitudinally. APOE ε4 was significantly associated with higher PET-PiB retention and lower CSF Aβ1-42, independent of age and sex, but APOE genotype did not significantly affect Aβ change over time. APOE ε4 carriers may be further along in the disease process, consistent with earlier brain Aβ deposition and providing a biological basis for APOE genotype effects on onset age of Alzheimer's disease.
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA. Electronic address: resnicks@mail.nih.gov.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
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.
authors.forename: Murat
authors.initials: M
authors.lastname: Bilgel
authors.affiliation: Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Abhay
authors.initials: A
authors.lastname: Moghekar
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 Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Mei-Cheng
authors.initials: MC
authors.lastname: Wang
authors.affiliation: Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Madhav
authors.initials: M
authors.lastname: Thambisetty
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Prince
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 Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: Soldan
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 Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Brien
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: Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Marilyn S
authors.initials: MS
authors.lastname: Albert
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D002250:Carbon Radioisotopes; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D013844:Thiazoles; C075222:amyloid beta-protein (1-42)
keywords: Apolipoprotein E genotype; Biomarkers; CSF Aβ(1-42); Longitudinal; PET amyloid imaging