title: CSF Aβ42 predicts early-onset dementia in Parkinson disease.
abstract: OBJECTIVE
  To test in vivo the proposal from clinicopathologic studies that β-amyloid (Aβ) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF Aβ and related measures as early prognostic biomarkers of dementia in an incident PD cohort.
  
  
  METHODS
  We assessed a population-based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis. We analyzed CSF concentrations of Aβ42, Aβ40, and Aβ38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of Aβ42, total tau, and phosphorylated tau using ELISA. Patients were followed prospectively for 5 years. Dementia was diagnosed according to published criteria.
  
  
  RESULTS
  CSF levels of Aβ42 were significantly decreased in patients who developed dementia (n = 20, 19.2%) compared to those who did not (n = 84, 80.8%), as measured by ECL (-33%, p = 0.006) as well as ELISA (-36%, p < 0.001). No differences were observed for other markers. Low Aβ42 values predicted a substantially increased risk for subsequent dementia at high sensitivity (≥ 85%), with hazard ratios of 9.9 (95% confidence interval 2.3-43.5, p = 0.002) for Aβ42ECL <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for Aβ42ELISA <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. Aβ42 reductions tended to precede the onset of PD-MCI that progressed to dementia.
  
  
  CONCLUSIONS
  These in vivo data support the role of Aβ pathology in the etiology and highlight the potential utility of CSF Aβ42 as an early prognostic biomarker of dementia associated with PD.
authors.affiliation: From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway. algu@sus.no.
authors.forename: Guido
authors.initials: G
authors.lastname: Alves
authors.affiliation: From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lange
authors.affiliation: From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway.
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.affiliation: From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway.
authors.forename: Marthe G
authors.initials: MG
authors.lastname: Førland
authors.affiliation: From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway.
authors.forename: Ole-Bjørn
authors.initials: OB
authors.lastname: Tysnes
authors.affiliation: From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Larsen
authors.affiliation: From The Norwegian Centre for Movement Disorders (G.A., J.L., M.G.F., J.P.L., K.F.P.), Department of Neurology (G.A., K.F.P.), and Memory Clinic (G.A., K.F.P.), Stavanger University Hospital, Norway; Institute of Neuroscience and Physiology (K.B., H.Z., U.A.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; the Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway; and the Network for Medical Sciences (J.P.L.), University of Stavanger, Norway.
authors.forename: Kenn F
authors.initials: KF
authors.lastname: Pedersen
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D003704:Dementia / Q000134:cerebrospinal fluid / Q000150:complications / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000150:complications*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011379:Prognosis; D012306:Risk
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)