CSF Aß42 predicts early-onset dementia in Parkinson disease.

ABSTRACT

OBJECTIVE: To test in vivo the proposal from clinicopathologic studies that ß-amyloid (Aß) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF Aß 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 Aß42, Aß40, and Aß38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of Aß42, 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 Aß42 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 Aß42 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 Aß42ECL <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for Aß42ELISA <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. Aß42 reductions tended to precede the onset of PD-MCI that progressed to dementia. CONCLUSIONS: These in vivo data support the role of Aß pathology in the etiology and highlight the potential utility of CSF Aß42 as an early prognostic biomarker of dementia associated with PD.