Cerebrospinal fluid amyloid-β and phenotypic heterogeneity in de novo Parkinson's disease
- Guido Alves1,2,
- Kenn Freddy Pedersen1,2,
- Bastiaan R Bloem3,
- Kaj Blennow4,
- Henrik Zetterberg4,
- George F Borm5,
- Turi O Dalaker1,6,
- Mona K Beyer1,6,
- Dag Aarsland7,
- Ulf Andreasson4,
- Johannes Lange1,
- Ole-Bjørn Tysnes8,
- Robert Zivadinov9,
- Jan Petter Larsen1
- 1The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway
- 2Department of Neurology, Stavanger University Hospital, Stavanger, Norway
- 3Department of Neurology, Radboud University Nijmegen Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
- 4Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden
- 5Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
- 6Department of Radiology, Stavanger University Hospital, Stavanger, Norway
- 7Department of Psychiatry, Stavanger University Hospital, Stavanger, Norway
- 8Department of Neurology, Haukeland University Hospital, Bergen, Norway
- 9Buffalo Neuroimaging Analysis Center, The Jakobs Neurological Institute, State University of New York, Buffalo, New York, USA
- Correspondence to Dr Guido Alves, The Norwegian Centre for Movement Disorders, Stavanger University Hospital, PO Box 8100, Stavanger N-4068, Norway;
- Received 30 July 2012
- Revised 2 October 2012
- Accepted 4 October 2012
- Published Online First 31 October 2012
Background In Parkinson's disease (PD), the motor presentation characterised by postural instability/gait difficulties (PIGD) heralds accelerated motor, functional and cognitive decline, as compared with the more benign tremor-dominant (TD) variant. This makes the PIGD complex an attractive target for the discovery of prognostic biomarkers in PD.
Objective To explore in vivo whether variability in brain amyloid-β (Aβ) metabolism affects the initial motor presentation in PD.
Methods We quantified cerebrospinal fluid (CSF) concentrations and ratios of Aβ42, Aβ40 and Aβ38 using a triplex immunoassay in 99 patients with de novo PD with the PIGD phenotype (n=39) or the TD phenotype (n=60). All patients underwent standardised assessments of motor and neuropsychological function and cerebral MRI. 46 age-matched normal controls served as external reference.
Results Patients with PD with the PIGD phenotype had significantly reduced CSF Aβ42, Aβ38, Aβ42/40 and Aβ38/40 levels compared with patients with the TD phenotype and controls. CSF marker levels in patients with PD-TD did not differ from those in controls. Multivariate regression models demonstrated significant associations of CSF Aβ markers with severity of PIGD and lower limb bradykinesia in patients with PD, independently from age, MRI white matter hyperintensities and cognition. No associations were found between CSF markers and other motor features.
Conclusions Motor heterogeneity in de novo PD independently relates to CSF Aβ markers, with low levels found in patients with the PIGD presentation. This suggests that disturbed Aβ metabolism has an effect on PD beyond cognition and may contribute to the variable rate of motor and functional decline in PD.