title: Cerebrospinal fluid Aβ42 is the best predictor of clinical progression in patients with subjective complaints.
abstract: BACKGROUND
  The need to recognize Alzheimer's disease (AD) as early as possible led us to evaluate the predictive value of amyloid β(1-42) (Aβ42), total tau (tau), and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) for clinical progression in patients with subjective complaints.
  
  
  METHODS
  We recruited nondemented patients with subjective complaints (i.e., criteria for mild cognitive impairment [MCI] not fulfilled) from our memory clinic. We assessed the predictive value of CSF Aβ42, tau, and ptau for clinical progression using Cox proportional hazards models adjusted for age, gender, and baseline findings on the Mini-Mental State Examination (MMSE). Clinical progression was defined as progression to MCI or AD.
  
  
  RESULTS
  We included 127 patients with subjective complaints (age 60 ± 10 years, 61 [48%] females, MMSE 29 ± 1). At baseline, Aβ42 and tau were abnormal in 20 patients (both 16%), and ptau in 32 patients (25%). Thirteen patients (10%) progressed to MCI (n = 11) or AD (n = 2). Aβ42 was the strongest predictor of progression to MCI or AD with an adjusted hazard ratio (HR) of 16.0 (3.8-66.4). The adjusted HR associated with tau was 2.8 (0.9-9.2) and with ptau 2.6 (0.8-8.2). Combinations of biomarkers had a lower predictive value than Aβ42 alone.
  
  
  CONCLUSIONS
  Low Aβ42 was the strongest predictor of clinical progression in patients with subjective complaints. These results are in line with the hypothesis that the cascade of pathologic events starts with deposition of Aβ42, whereas neuronal degeneration and hyperphosphorylation of tau are more downstream events, closer to clinical manifestation of AD.
authors.affiliation: Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands. a.vanharten@vumc.nl
authors.forename: Argonde C
authors.initials: AC
authors.lastname: van Harten
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins