CSF Aβ42 predicts early-onset dementia in Parkinson disease

Guido Alves; Johannes Lange; Kaj Blennow; Henrik Zetterberg; Ulf Andreasson; Marthe G Førland; Ole-Bjørn Tysnes; Jan P Larsen; Kenn F Pedersen

doi:10.1212/WNL.0000000000000425

CSF Aβ42 predicts early-onset dementia in Parkinson disease

Neurology. 2014 May 20;82(20):1784-90. doi: 10.1212/WNL.0000000000000425. Epub 2014 Apr 18.

Authors

Guido Alves¹, Johannes Lange², Kaj Blennow², Henrik Zetterberg², Ulf Andreasson², Marthe G Førland², Ole-Bjørn Tysnes², Jan P Larsen², Kenn F Pedersen²

Affiliations

¹ 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.
² 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.

PMID: 24748671
DOI: 10.1212/WNL.0000000000000425

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Amyloid beta-Peptides / cerebrospinal fluid*
Dementia / cerebrospinal fluid
Dementia / complications
Dementia / diagnosis*
Female
Humans
Male
Middle Aged
Parkinson Disease / cerebrospinal fluid
Parkinson Disease / complications*
Peptide Fragments / cerebrospinal fluid*
Prognosis
Risk

Substances

Amyloid beta-Peptides
Peptide Fragments
amyloid beta-protein (1-42)