Cerebrospinal Fluid Aβ Levels Correlate With Structural Brain Changes in Parkinson's Disease.

Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
Movement Disorders (Impact Factor: 5.68). 03/2013; 28(3). DOI: 10.1002/mds.25282
Source: PubMed


ParkWest is a large Norwegian multicenter study of newly diagnosed drug-naïve subjects with Parkinson's disease (PD). Cognitively normal PD subjects (PDCN) and PD subjects with mild cognitive impairment (PDMCI) from this cohort have significant hippocampal atrophy and ventricular enlargement, compared to normal controls. Here, we aimed to investigate whether the same structural changes are associated with cerebrospinal fluid (CSF) levels of amyloid beta (Aβ)(38) , Aβ(40) , Aβ(42) , total tau (t-tau), and phosphorylated tau (p-tau). We performed three-dimensional radial distance analyses of the hippocampi and lateral ventricles using the MRI data from ParkWest subjects who provided CSF at baseline. Our sample consisted of 73 PDCN and 18 PDMCI subjects. We found significant associations between levels of all three CSF Aβ analytes and t-tau and lateral ventricular enlargement in the pooled sample. In the PDCN sample, all three amyloid analytes showed significant associations with the radial distance of the occipital and frontal horns of the lateral ventricles. CSF Aβ(38) and Aβ(42) showed negative associations, with enlargement in occipital and frontal horns of the lateral ventricles in the pooled sample, and a negative association with the occipital horns in PDMCI. CSF Aβ levels in early PD correlate with ventricular enlargement, previously associated with PD dementia. Therefore, CSF and MRI markers may help identify PD patients at high risk for developing cognitive decline and dementia in the course of their illness. Contrary to Alzheimer's disease, we found no associations between CSF t-tau and p-tau and hippocampal atrophy. © 2013 Movement Disorder Society.

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    • "Although BCHE K+ |APOE ␧4+ individuals may be more likely to develop DLB than PDD, carriers of these alleles with PD are more likely to develop dementia at an earlier age and stage of their movement disorder [34]. While loss of dopamine neurotransmission and cortical ␣-synuclein pathology may contribute to cognitive impairment and dementia, PD patients with the highest burden of cortical A␤ plaques and/or lowest levels of CSF A␤ 42 have the fastest progression of cognitive (but not motor) decline, incident dementia, and Alzheimer-like structural brain changes [83] [84] [85] [86]. These patients also have highest CSF levels of ApoE [87]. "
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    • "Because there is much evidence on the contribution of oxidative stress in the pathogenesis of PD (Figure 1) (Alonso-Navarro et al., 2008), the measurement of oxidative stress markers and substances related with oxidative and defense against oxidative phenomena in the CSF of PD patients is useful. Data regarding lipid peroxidation markers are controversial, while DNA oxidation markers have been found to be increased (Table 3). "
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    Frontiers in Cellular Neuroscience 11/2014; fncel.2014.00369. eCollection 2014.. DOI:10.3389/fncel.2014.00369 · 4.29 Impact Factor
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    • "The findings of current study indicate increased ventricular size in the brain of mice treated with MPTP. Larger ventricular size is one of the indicators of cognitive impairment in late Parkinson's subjects (Lewis et al. 2009; Dalaker et al. 2011; Beyer et al. 2013). The finding of increased ventricular size with MPTP exposure suggests progression of PD in mice in line with the sporadic PD. "
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