title: Role of family history for Alzheimer biomarker abnormalities in the adult children study.
abstract: OBJECTIVE
  To assess whether family history (FH) of Alzheimer disease (AD) alone influences AD biomarker abnormalities.
  
  
  METHODS
  Adult Children Study.
  
  
  METHODS
  Washington University's Charles F. and Joanne Knight Alzheimer's Disease Research Center.
  
  
  METHODS
  A total of 269 cognitively normal middle- to older-aged individuals with and without an FH for AD.
  
  
  METHODS
  Clinical and cognitive measures, magnetic resonance imaging-based brain volumes, diffusion tensor imaging-based white matter microstructure, cerebrospinal fluid biomarkers, and molecular imaging of cerebral fibrillar amyloid with positron emission tomography using the [(11)C] benzothiazole tracer, Pittsburgh compound B.
  
  
  RESULTS
  A positive FH for AD was associated with an age-related decrease of cerebrospinal fluid Aβ42; the ε4 allele of apolipoprotein E (APOE4) did not alter this effect. Age-adjusted cerebrospinal fluid Aβ42 was decreased for individuals with APOE4 compared with the level for those without, and the decrease was larger for individuals with a positive FH compared with the decrease for those without. The variation of cerebrospinal fluid tau and Pittsburgh compound B mean cortical binding potential increased by age. For individuals younger than 55, an age-related increase in mean cortical binding potential was associated with APOE4 but not FH. For individuals older than 55, a positive FH and a positive APOE4 implied the fastest age-related increase in mean cortical binding potential. A positive FH was associated with decreased fractional anisotropy from diffusion tensor imaging in the genu and splenium of the corpus callosum.
  
  
  CONCLUSIONS
  Independent of APOE4, FH is associated with age-related change of several cerebrospinal fluid, Pittsburgh compound B, and diffusion tensor imaging biomarkers in cognitively normal middle- to older-aged individuals, suggesting that non- APOE susceptibility genes for AD influence AD biomarkers.
authors: Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, Missouri, USA. chengjie@wubios.wustl.edu
authors: Chengjie
authors: C
authors: Xiong
authors: Catherine M
authors: CM
authors: Roe
authors: Virginia
authors: V
authors: Buckles
authors: Anne
authors: A
authors: Fagan
authors: David
authors: D
authors: Holtzman
authors: David
authors: D
authors: Balota
authors: Janet
authors: J
authors: Duchek
authors: Martha
authors: M
authors: Storandt
authors: Mark
authors: M
authors: Mintun
authors: Elizabeth
authors: E
authors: Grant
authors: Abraham Z
authors: AZ
authors: Snyder
authors: Denise
authors: D
authors: Head
authors: Tammie L S
authors: TL
authors: Benzinger
authors: Joseph
authors: J
authors: Mettenburg
authors: John
authors: J
authors: Csernansky
authors: John C
authors: JC
authors: Morris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D001288:Attention / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002250:Carbon Radioisotopes; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D015331:Cohort Studies; D018450:Disease Progression; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000502:physiology; D012111:Residence Characteristics; D013223:Statistics as Topic; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D015415:Biomarkers; D002250:Carbon Radioisotopes; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42)