Showing papers by "Pietro Tiraboschi published in 2019"
TL;DR: This study provides the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities for α-synuclein, and suggests RT-QuIC analyses of OM and cerebrospinal fluid (CSF) can be combined with the aim of increasing the overall diagnostic accuracy of these diseases.
Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms. PD is characterized by intraneuronal accumulation of abnormal α-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of either α-synuclein, as in the case of Multiple System Atrophy (MSA) or tau, as in the case of Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP), in other disease-specific brain regions. Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization of α-synuclein or tau aggregates in the brain. Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues, including receptor neurons of the olfactory mucosa (OM). We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion (RT-QuIC) assay for OM analysis. In particular, by using human recombinant α-synuclein as substrate of reaction, we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induce α-synuclein aggregation, and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP. Our results showed that a significant percentage of MSA and PD samples induced α-synuclein aggregation with high efficiency, but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect. Notably, the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination. Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities for α-synuclein. Additional studies are required for (i) estimating sensitivity and specificity of the technique and for (ii) evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms. RT-QuIC analyses of OM and cerebrospinal fluid (CSF) can be combined with the aim of increasing the overall diagnostic accuracy of these diseases, especially in the early stages.
94 citations
University of Cambridge1, Erasmus University Rotterdam2, University of Brescia3, University of Milan4, University of Toronto5, Sunnybrook Research Institute6, Sunnybrook Health Sciences Centre7, Karolinska University Hospital8, Karolinska Institutet9, University of Geneva10, Laval University11, University of Western Ontario12, University of Lisbon13, University of Florence14, UCL Institute of Neurology15, University of Coimbra16, University of Ulm17, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico18, University of Tübingen19, Katholieke Universiteit Leuven20, University of Manchester21, McGill University22, Ludwig Maximilian University of Munich23, Toronto Rehabilitation Institute24, University of London25, University of Amsterdam26, Mayo Clinic27, University Health Network28, University of Oxford29
TL;DR: It is proposed that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically.
37 citations
King's College London1, UCL Institute of Neurology2, University College London3, Erasmus University Rotterdam4, University of Barcelona5, University of Brescia6, Laval University7, Sunnybrook Health Sciences Centre8, University of Toronto9, Karolinska University Hospital10, University of Milan11, University of Cambridge12, University of Western Ontario13, University of Tübingen14, Katholieke Universiteit Leuven15, University of Lisbon16, University of Coimbra17, McGill University Health Centre18, University of Oxford19, University of Manchester20, Ludwig Maximilian University of Munich21, University of Florence22, University of Ulm23
TL;DR: Investigation of longitudinal change in WMH and the associations of WMH burden with grey matter (GM) loss, markers of neurodegeneration and cognitive function in GRN mutation carriers revealed that WMH load was higher in both symptomatic and presymptomatic groups compared with controls and this load increased over time.
29 citations
TL;DR: Conurrent impairment of Corsi span and semantic verbal fluency, or of temporal lobe hypometabolism at baseline and reduced putamen-to-caudate ratio on DAT-SPECT at parkinsonism onset, both predicted the evolution to dementia.
19 citations
UCL Institute of Neurology1, University College London2, University of Paris3, French Institute for Research in Computer Science and Automation4, University of London5, Erasmus University Rotterdam6, University of Brescia7, University of Milan8, Sunnybrook Health Sciences Centre9, University of Toronto10, University of Cambridge11, Karolinska Institutet12, Karolinska University Hospital13, Laval University14, University of Western Ontario15, University of Lisbon16, University of Florence17, King's College London18, Sunnybrook Research Institute19, University of Coimbra20, University Health Network21, Mayo Clinic22
TL;DR: A spatiotemporal analysis pipeline based on Large Diffeomorphic Deformation Metric Mapping (LDDMM) to detect shape changes from volumetric MRI scans is proposed and found statistical differences in shape in the anterior region of the thalamus at least five years before the mutation carrier subjects develop any clinical symptoms.
17 citations
TL;DR: A comprehensive evaluation of the role of molecular imaging in the frame of the revised DLB criteria is presented and a critical summary of the current state of the art in pathological validation of other biomarkers including amyloid and tau-PET imaging is provided.
Abstract: Recommendations about clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) have been recently refined by the DLB Consortium. Substantial new information has been incorporated with increased diagnostic weighting given to molecular imaging biomarkers. The present work attempted to present a comprehensive evaluation of the role of molecular imaging in the frame of the revised DLB criteria. To this end, we briefly review the molecular imaging tools in the fourth Consensus report of the DLB Consortium, highlighting several indicative and supportive surrogate markers, including I-123 brain dopamine transporter (DaT), I-123 mIBG cardiac norepinephrine transporter (NeT) and brain F-18 fluorodeoxyglucose (FDG) imaging, as the main way to increase accuracy of ante-mortem diagnosis of probable or possible DLB. Along with main neuropathological and clinical issues, we focus on the diagnostic performance and appropriate use of current available items included in the index by nuclear medicine physicians, namely a low DaT uptake, a low NeT expression in myocardial tissue, and reduced parieto-occipital metabolism on brain FDG-PET. Moreover, a critical summary of the current state of the art in pathological validation of other biomarkers including amyloid and tau-PET imaging is provided. DLB Consortium clearly states that clinical diagnosis in clinical routine is suboptimal and gives more weight to molecular imaging biomarkers to offer a more objective information. Along with DaT, mIBG and FDG techniques, brain PET with more specific radiotracers could open a new scenario for an accurate evaluation of biomarkers involved in DLB.
3 citations
TL;DR: In the article mentioned above all authors were assigned affiliation 14, which is wrong, which belongs only to author Agostino Chiaravalloti.
Abstract: In the article mentioned above all authors were assigned affiliation 14, which is wrong. Affiliation 14 belongs only to author Agostino Chiaravalloti.
1 citations