title: Amyloid-β--associated clinical decline occurs only in the presence of elevated P-tau.
abstract: OBJECTIVE
  To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-(Aβ) and tau, and clinical decline over time among cognitively normal older individuals.
  
  
  METHODS
  A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments.
  
  
  METHODS
  Research centers across the United States and Canada.
  
  
  METHODS
  We examined 107 participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination.
  
  
  METHODS
  Using linear mixed effects models, we investigated the relationship between cerebrospinal fluid (CSF) phospho-tau 181 (p-tau(181p)),CSF Aβ(1-42), and clinical decline as assessed using longitudinal change in global CDR, CDR-Sum of Boxes, and the Alzheimer Disease Assessment Scale-cognitive subscale.
  
  
  RESULTS
  We found a significant relationship between decreased CSF Aβ(1-42) and longitudinal change in global CDR,CDR-Sum of Boxes, and Alzheimer Disease Assessment Scale-cognitive subscale in individuals with elevated CSFp-tau(181p). In the absence of CSF p-tau(181p), the effect of CSF Aβ(1-42) on longitudinal clinical decline was not significantly different from 0.
  
  
  CONCLUSIONS
  In cognitively normal older individuals,A-associated clinical decline during a mean of 3 years may occur only in the presence of ongoing downstream neurodegeneration.
authors.affiliation: Department of Radiology, University of California–San Diego, 8950 Villa La Jolla Dr, Ste C101, La Jolla, CA 92037-0841, USA. rdesikan@ucsd.edu
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Desikan
authors.forename: Linda K
authors.initials: LK
authors.lastname: McEvoy
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Thompson
authors.forename: Dominic
authors.initials: D
authors.lastname: Holland
authors.forename: James B
authors.initials: JB
authors.lastname: Brewer
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011569:Psychiatric Status Rating Scales; D014481:United States / Q000453:epidemiology; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins