title: Amyloid-β oligomers relate to cognitive decline in Alzheimer's disease.
abstract: BACKGROUND
  Amyloid-β (Aβ)-oligomers are neurotoxic isoforms of Aβ and are a potential diagnostic biomarker for Alzheimer's disease (AD).
  
  
  OBJECTIVE
  1) Analyze the potential of Aβ-oligomer concentrations in cerebrospinal fluid (CSF) to diagnose and predict progression to AD in a large clinical study sample. 2) Monitor Aβ-oligomer concentrations over-time, both in early and advanced stages of AD. 3) Examine the relation between Aβ-oligomer levels in CSF and cognitive functioning.
  
  
  METHODS
  24 non-demented, 61 mild cognitive impairment (MCI), and 64 AD patients who underwent lumbar puncture and cognitive testing at baseline and follow-up were selected from the memory clinic based Amsterdam Dementia Cohort. CSF samples were analyzed for standard AD-biomarkers and Aβ-oligomer levels using a validated in-house Aβ-oligomer specific enzyme-linked immunosorbent assay. Aβ-oligomer levels were analyzed as indicators of disease progression (follow-up AD diagnosis) and cognitive decline, respectively.
  
  
  RESULTS
  Patient groups did not differ in Aβ-oligomer concentrations at baseline or follow-up. Baseline CSF Aβ-oligomer levels were similar in MCI patients that develop AD as in stable MCI patients. MCI and AD patients showed an annual decrease in Aβ-oligomer levels of 9.4% and 6.8%, respectively. A decrease in Aβ-oligomer levels over time was strongly associated with more severe cognitive decline in AD patients.
  
  
  CONCLUSIONS
  Despite the limited diagnostic potential of Aβ-oligomer levels in CSF to differentiate between patient groups, and between MCI-AD and MCI-stable patients, changes in CSF Aβ-oligomer levels were related to cognitive decline. Therefore, CSF Aβ-oligomers may aid in the selection of patients with a more aggressive disease course.
authors.affiliation: Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wesley
authors.initials: W
authors.lastname: Jongbloed
authors.affiliation: Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and behaviour, Alzheimer Centre Nijmegen, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Bruggink
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Maartje I
authors.initials: MI
authors.lastname: Kester
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Pieter-Jelle
authors.initials: PJ
authors.lastname: Visser
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.affiliation: Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and behaviour, Alzheimer Centre Nijmegen, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
authors.affiliation: Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.affiliation: Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Veerhuis
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D013223:Statistics as Topic
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; amyloid-β peptides; biological markers; cerebrospinal fluid; cognition; dementia; disease progression; mild cognitive impairment