Distinct functional and macrostructural brain changes in Parkinson's disease and multiple system atrophy.
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ABSTRACT:
SUBMITTER: Planetta PJ
PROVIDER: S-EPMC4950674 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Multiple system atrophy (MSA) and Parkinson's disease (PD) belong to alpha-synucleinopathy, but they have very different clinical courses and prognoses. An imaging biomarker that can differentiate between the two diseases early in the disease course is desirable for appropriate treatment. Neuroimaging-based brain age paradigm provides an individualized marker to differentiate aberrant brain aging patterns in neurodegenerative diseases. In this study, patients with MSA (N = 23), PD (N = 33), and healthy controls (N = 34; HC) were recruited. A deep learning approach was used to estimate brain-predicted age difference (PAD) of gray matter (GM) and white matter (WM) based on image features extracted from T1-weighted and diffusion-weighted magnetic resonance images, respectively. Spatial normative models of image features were utilized to quantify neuroanatomical impairments in patients, which were then used to estimate the contributions of image features to brain age measures. For PAD of GM (GM-PAD), patients with MSA had significantly older brain age (9.33 years) than those with PD (0.75 years; P = 0.002) and HC (-1.47 years; P < 0.001), and no significant difference was found between PD and HC (P = 1.000). For PAD of WM (WM-PAD), it was significantly greater in MSA (9.27 years) than that in PD (1.90 years; P = 0.037) and HC (-0.74 years; P < 0.001); there was no significant difference between PD and HC (P = 0.087). The most salient image features that contributed to PAD in MSA and PD were different. For GM, they were the orbitofrontal regions and the cuneus in MSA and PD, respectively, and for WM, they were the central corpus callosum and the uncinate fasciculus in MSA and PD, respectively. Our results demonstrated that MSA revealed significantly greater PAD than PD, which might be related to markedly different neuroanatomical contributions to brain aging. The image features with distinct contributions to brain aging might be of value in the differential diagnosis of MSA and PD.
| S-EPMC8987993 | biostudies-literature
Project description:MicroRNAs (miRNAs) are endogenous small (18-25 nt), single-stranded, non-coding RNAs that play key roles in post-transcriptional gene expression regulation. The expression profiles of miRNAs in biofluids and tissues change in various diseases. Multiple system atrophy (MSA) and Parkinson's disease (PD) are both categorized as α-synucleinopathies and often present with similar clinical manifestations. This study aimed to identify miRNAs that are differently expressed in plasma samples of PD patients, MSA patients, and healthy controls. We used microarray analysis to screen for miRNAs that are up- and down-regulated in these patients and analyzed the relative-quantitative expression levels of the identified miRNAs by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p showed significantly different expression levels among patients with MSA-C, MSA-P, or PD, and healthy controls. Hsa-miR-671-5p levels were lower in the MSA-P and PD than the MSA-C and control groups, hsa-miR-19b-3p levels were higher in the PD than the other groups, and hsa-miR-24-3p levels were higher in the PD than the MSA-C group. Hsa-miR-671-5p was the first miRNA shown to be expressed differently between MSA-C and MSA-P in plasma. Interestingly, the expression levels of hsa-miR-19b-3p and hsa-miR-24-3p were positively correlated, indicating that these miRNAs may be involved in the same processes in PD pathogenesis. Our findings suggest that hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p may reflect the pathophysiology or symptoms of PD and MSA.
| S-EPMC6518614 | biostudies-literature
Project description:Aggregation of alpha-synuclein (α-syn) is considered to be the major pathological hallmark and driving force of Multiple System Atrophy (MSA) and Parkinson's disease (PD). Immune dysfunctions have been associated with both MSA and PD and recently we reported that the levels of natural occurring autoantibodies (NAbs) with high-affinity/avidity toward α-synuclein are reduced in MSA and PD patients. Here, we aimed to evaluate the plasma immunoglobulin (Ig) composition binding α-syn and other amyloidogenic neuropathological proteins, and to correlate them with disease severity and duration in MSA and PD patients. All participants were recruited from a single neurological unit and the plasma samples were stored for later research at the Bispebjerg Movement Disorder Biobank. All patients were diagnosed according to current consensus criteria. Using multiple variable linear regression analyses, we observed higher levels of anti-α-syn IgG1 and IgG3 NAbs in MSA vs. PD, higher levels of anti-α-syn IgG2 NAbs in PD compared to controls, whereas anti-α-syn IgG4 NAbs were reduced in PD compared to MSA and controls. Anti-α-syn IgM levels were decreased in both MSA and PD. Further our data supported that MSA patients' immune system was affected with reduced IgG1 and IgM global levels compared to PD and controls, with further reduced global IgG2 levels compared to PD. These results suggest distinct autoimmune patterns in MSA and PD. These findings suggest a specific autoimmune physiological mechanism involving responses toward α-syn, differing in neurodegenerative disease with overlapping α-syn pathology.
| S-EPMC6769034 | biostudies-literature
Project description:Pareidolia is a visual illusion of meaningful objects that arise from ambiguous forms embedded in visual scenes. Previous studies showed that pareidolias are frequently observed in patients with Parkinson's disease (PD) as well as dementia with Lewy bodies. However, whether pareidolias are useful for differentiating PD from other neurodegenerative parkinsonism disorders including multiple system atrophy (MSA) is unclear. The noise pareidolia test (NPT) was performed in 40 and 48 patients with PD and MSA, respectively. A receiver operating characteristic (ROC) curve analysis was used to evaluate sensitivity and specificity. Results of neuropsychological tests were also compared between patients with PD with and without pareidolias. Visual hallucinations were present in none of the subjects. Pareidolic response in the NPT was observed in 47.5% and 18.8% of patients with PD and MSA, respectively. The number of pareidolic responses in patients with PD was significantly larger compared with patients with MSA (P=0.001). ROC curve analyses showed the sensitivity and specificity at 33% and 98%, respectively. Among patients with PD, those with pareidolias demonstrated higher State-Trait Anxiety Inventory-state (P=0.044) and State-Trait Anxiety Inventory-trait (P=0.044) than those without pareidolias. Pareidolias can be found in patients with PD without visual hallucinations, and the pareidolia test may be a highly specific test for differentiating PD from MSA. Thus, anxiety may be associated with pareidolias in patients with PD.
| S-EPMC8572613 | biostudies-literature
Project description:ObjectiveConverging evidence suggests that intestinal inflammation is involved in the pathogenesis of neurodegenerative diseases. Previous studies on fecal calprotectin in Parkinson's disease (PD) were limited by small sample sizes, and literature regarding intestinal inflammation in multiple system atrophy (MSA) is very scarce. We investigated the levels of fecal calprotectin, a marker of intestinal inflammation, in PD and MSA.MethodsWe recruited 169 subjects (71 PD, 38 MSA, and 60 age-similar nonneurological controls). Clinico-demographic data were collected. PD and MSA were subtyped and the severity assessed using the MDS-UPDRS and UMSARS, respectively. Fecal calprotectin and blood immune markers were analyzed.ResultsCompared to controls (median: 35.7 [IQR: 114.2] μg/g), fecal calprotectin was significantly elevated in PD (median: 95.6 [IQR: 162.1] μg/g, p = 0.003) and even higher in MSA (median: 129.5 [IQR: 373.8] μg/g, p = 0.002). A significant interaction effect with age was observed; between-group differences were significant only in older subjects (i.e., ≥ 61 years) and became more apparent with increasing age. A total of 28.9% of MSA and 18.3% of PD patients had highly abnormal fecal calprotectin levels (≥ 250 μg/g); however, this difference was only significant for MSA compared to controls. Fecal calprotectin correlated moderately with selected blood immune markers in PD, but not with clinical features of PD or MSA.Conclusions Elevated fecal calprotectin suggests a role for intestinal inflammation in PD and MSA. A more complete understanding of gut immune alterations could open up new avenues of research and treatment for these debilitating diseases.
| S-EPMC9171316 | biostudies-literature
Project description:BackgroundBoth Parkinson's disease (PD) and multiple system atrophy (MSA) exhibit degeneration of brainstem serotoninergic nuclei, affecting multiple subcortical and cortical serotoninergic projections. In MSA, medullary serotoninergic neuron pathology is well documented, but serotonin system changes throughout the rest of the brain are less well characterized.ObjectivesTo use serotonin transporter [11 C]3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile positron emission tomography (PET) to compare serotoninergic innervation in patients with MSA and PD.MethodsWe performed serotonin transporter PET imaging in 18 patients with MSA, 23 patients with PD, and 16 healthy controls to explore differences in brainstem, subcortical, and cortical regions of interest.ResultsPatients with MSA showed lower serotonin transporter distribution volume ratios compared with patients with PD in the medulla, raphe pontis, ventral striatum, limbic cortex, and thalamic regions, but no differences in the dorsal striatal, ventral anterior cingulate, or total cortical regions. Controls showed greater cortical serotonin transporter binding compared with PD or MSA groups but lower serotonin transporter binding in the striatum and other relevant basal ganglia regions. There were no regional differences in binding between patients with MSA-parkinsonian subtype (n = 8) and patients with MSA-cerebellar subtype (n = 10). Serotonin transporter distribution volume ratios in multiple different regions of interest showed an inverse correlation with the severity of Movement Disorders Society Unified Parkinson's Disease Rating Scale motor score in patients with MSA but not patients with PD.ConclusionsBrainstem and some forebrain subcortical region serotoninergic deficits are more severe in MSA compared with PD and show an MSA-specific correlation with the severity of motor impairments. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC9669145 | biostudies-literature
Project description:Background and purposeThe eye-movement examination can be applied as a noninvasive method to identify multiple-system atrophy (MSA). Few studies have investigated eye movements during the early stage of MSA with predominant parkinsonism (MSA-P). We aimed to determine the characteristic oculomotor changes in the early stage of MSA-P.MethodsWe retrospectively selected 17 patients with MSA-P and 40 with Parkinson's disease (PD) with disease durations of less than 2 years, and 40 age-matched healthy controls (HCs). Oculomotor performance in the horizontal direction was measured in detail using videonystagmography.ResultsWe found that the proportions of patients with MSA-P and PD exhibiting abnormal eye movements were 82.4% and 77.5%, respectively, which were significantly higher than that in the HCs (47.5%, p<0.05). Compared with HCs, patients with MSA-P presented significantly higher abnormal proportions of fixation and gaze-holding (17.6% vs. 0%), without-fixation (47.1% vs. 0%), prolonged latency in reflexive saccades (29.4% vs. 5.0%), memory-guided saccades (93.3% vs. 10.0%), and catch-up saccades in smooth-pursuit movement (SPM, 41.2% vs. 0) (all p<0.05). Compared with those with PD, patients with MSA-P presented a significantly higher proportion of catch-up saccades in SPM (41.2% vs. 2.5%, p<0.001).ConclusionsMSA-P presented the characteristic of catch-up saccades in SPM in the early stage, which may provide some value in differentiating MSA-P from PD.
| S-EPMC10782091 | biostudies-literature
Project description:BackgroundGait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls.ObjectivesWe compared gait variability at different walking velocities between and within groups of patients with Parkinson-variant multiple system atrophy, idiopathic Parkinson's disease, and a control group of older adults.MethodsGait metrics were recorded in 11 multiple system atrophy, 12 Parkinson's disease patients, and 18 controls using sensor-based gait analysis. Gait variability was analyzed for stride, swing and stance time, stride length and gait velocity. Values were compared between and within the groups at self-paced comfortable, fast and slow walking speed.ResultsMultiple system atrophy patients displayed higher gait variability except for stride time at all velocities compared with controls, while Parkinson's patients did not. Compared with Parkinson's disease, multiple system atrophy patients displayed higher variability of swing time, stride length and gait velocity at comfortable speed and at slow speed for swing and stance time, stride length and gait velocity (all P < 0.05). Stride time variability was significantly higher in slow compared to comfortable walking in patients with multiple system atrophy (P = 0.014). Variability parameters significantly correlated with the postural instability/gait difficulty subscore in both disease groups. Conversely, significant correlations between variability parameters and MDS-UPDRS III score was observed only for multiple system atrophy patients.ConclusionThis analysis suggests that gait variability parameters reflect the major axial impairment and postural instability displayed by multiple system atrophy patients compared with Parkinson's disease patients and controls.
| S-EPMC8068710 | biostudies-literature
Project description:Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of α-synuclein, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy1. Clinically, it is challenging to differentiate Parkinson's disease and multiple system atrophy, especially at the early stages of disease2. Aggregates of α-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of α-synuclein that can self-propagate and spread from cell to cell3-6. Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect α-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity7,8. Here we show that the α-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson's disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of α-synuclein-PMCA, and found that the characteristics of the α-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson's disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that α-synuclein aggregates that are associated with Parkinson's disease and multiple system atrophy correspond to different conformational strains of α-synuclein, which can be amplified and detected by α-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of α-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson's disease and multiple system atrophy.
| S-EPMC7066875 | biostudies-literature
Project description:Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) are neurodegenerative disorders with alpha-synuclein (α-syn) aggregation pathology. Different strains of α-syn with unique properties are suggested to cause distinct clinical and pathological manifestations resulting in PD, MSA, or DLB. To study individual α-syn spreading patterns, we injected α-syn fibrils amplified from brain homogenates of two MSA patients and two PD patients into the brains of C57BI6/J mice. Antibody staining against pS129-α-syn showed that α-syn fibrils amplified from the brain homogenates of the four different patients caused different levels of α-syn spreading. The strongest α-syn pathology was triggered by α-syn fibrils of one of the two MSA patients, followed by comparable pS129-α-syn induction by the second MSA and one PD patient material. Histological analysis using an antibody against Iba1 further showed that the formation of pS129-α-syn is associated with increased microglia activation. In contrast, no differences in dopaminergic neuron numbers or co-localization of α-syn in oligodendrocytes were observed between the different groups. Our data support the spreading of α-syn pathology in MSA, while at the same time pointing to spreading heterogeneity between different patients potentially driven by individual patient immanent factors.
| S-EPMC10467043 | biostudies-literature