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CSF A beta(42) predicts early-onset dementia in Parkinson disease

Artikel i vetenskaplig tidskrift
Författare G. Alves
J. Lange
Kaj Blennow
Henrik Zetterberg
Ulf Andreasson
M. G. Forland
O. B. Tysnes
J. P. Larsen
K. F. Pedersen
Publicerad i Neurology
Volym 82
Nummer/häfte 20
Sidor 1784-1790
ISSN 0028-3878
Publiceringsår 2014
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 1784-1790
Språk en
Länkar dx.doi.org/10.1212/wnl.000000000000...
Ämnesord MILD COGNITIVE IMPAIRMENT, CEREBROSPINAL-FLUID BIOMARKERS, DIAGNOSTIC-CRITERIA, ALZHEIMERS-DISEASE, A-BETA, NORWEGIAN PARKWEST, AMYLOID-BETA, MOUSE MODEL, FOLLOW-UP, TAU, Clinical Neurology
Ämneskategorier Neurokemi

Sammanfattning

Objective:To test in vivo the proposal from clinicopathologic studies that -amyloid (A) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF A 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 A42, A40, and A38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of A42, 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 A42 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 A42 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 A42(ECL) <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for A42(ELISA) <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. A42 reductions tended to precede the onset of PD-MCI that progressed to dementia.Conclusions:These in vivo data support the role of A pathology in the etiology and highlight the potential utility of CSF A42 as an early prognostic biomarker of dementia associated with PD.

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