title: Imaging and cerebrospinal fluid biomarkers in early preclinical alzheimer disease.
abstract: Deposition of amyloid β (Aβ)-containing plaques as evidenced by amyloid imaging and cerebrospinal fluid (CSF) Aβ1-42 (Aβ42) is an early indicator of preclinical Alzheimer disease (AD). To better understand their relationship during the earliest preclinical stages, we investigated baseline CSF markers in cognitively normal individuals at different stages of amyloid deposition defined by longitudinal amyloid imaging with Pittsburgh compound B (PIB): (1) PIB-negative at baseline and follow-up (PIB(-) ; normal), (2) PIB-negative at baseline but PIB-positive at follow-up (PIB converters; early preclinical AD), and (3) PIB-positive at baseline and follow-up (PIB(+) ; preclinical AD).
  
  
  
  Cognitively normal individuals (n = 164) who had undergone baseline PIB scan and CSF collection within 1 year of each other and at least 1 additional PIB follow-up were included. Amyloid status was defined dichotomously using an a priori mean cortical cutoff.
  
  
  
  PIB converters (n = 20) at baseline exhibited significantly lower CSF Aβ42 compared to those who remained PIB-negative (n = 123), but higher compared to the PIB(+) group (n = 21). A robust negative correlation (r = -0.879, p = 0.0001) between CSF Aβ42 and absolute (but subthreshold) PIB binding was observed during this early preclinical stage. The negative correlation was not as strong once individuals were PIB-positive (r = -0.456, p = 0.038), and there was no correlation in the stable PIB(-) group (p = 0.905) or in the group (n = 10) with early symptomatic AD (p = 0.537).
  
  
  
  CSF Aβ42 levels are tightly coupled with cortical amyloid load in the earliest stages of preclinical AD, and begin to decrease dramatically prior to the point when an abnormal threshold of cortical accumulation is detected with amyloid imaging. Ann Neurol 2016;80:379-387.
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, MO. andrei@npg.wustl.edu.|Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO. andrei@npg.wustl.edu.|Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO. andrei@npg.wustl.edu.
authors.forename: Andrei G
authors.initials: AG
authors.lastname: Vlassenko
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO.
authors.forename: Lena
authors.initials: L
authors.lastname: McCue
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO.
authors.forename: Mateusz S
authors.initials: MS
authors.lastname: Jasielec
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, MO.
authors.forename: Yi
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, MO.|Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Gordon
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO.|Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.affiliation: Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO.|Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO.|Department of Neurology, Washington University School of Medicine, Saint Louis, MO.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, MO.|Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO.|Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO.
authors.forename: Tammie L S
authors.initials: TL
authors.lastname: Benzinger
authors.affiliation: Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO.|Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO.|Department of Neurology, Washington University School of Medicine, Saint Louis, MO.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO.|Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO.|Department of Neurology, Washington University School of Medicine, Saint Louis, MO.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000814:Aniline Compounds; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D062706:Prodromal Symptoms; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42)