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Regional differences in synaptic degeneration are linked to alpha-synuclein burden and axonal damage in Parkinson's disease and dementia with Lewy bodies.
Frigerio, Irene; Bouwman, Maud M A; Noordermeer, Ruby T G M M; Podobnik, Ema; Popovic, Marko; Timmermans, Evelien; Rozemuller, Annemieke J M; van de Berg, Wilma D J; Jonkman, Laura E.
Affiliation
  • Frigerio I; Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, 1081 HV, The Netherlands. i.frigerio@amsterdamumc.nl.
  • Bouwman MMA; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands. i.frigerio@amsterdamumc.nl.
  • Noordermeer RTGMM; Amsterdam Neuroscience, Brain imaging, Amsterdam, The Netherlands. i.frigerio@amsterdamumc.nl.
  • Podobnik E; Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, 1081 HV, The Netherlands.
  • Popovic M; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands.
  • Timmermans E; Amsterdam Neuroscience, Brain imaging, Amsterdam, The Netherlands.
  • Rozemuller AJM; Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, 1081 HV, The Netherlands.
  • van de Berg WDJ; Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1118, Amsterdam, 1081 HV, The Netherlands.
  • Jonkman LE; Department Molecular cell biology & Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, Netherlands.
Acta Neuropathol Commun ; 12(1): 4, 2024 Jan 03.
Article in En | MEDLINE | ID: mdl-38173031
ABSTRACT
Regional differences in synaptic degeneration may underlie differences in clinical presentation and neuropathological disease progression in Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Here, we mapped and quantified synaptic degeneration in cortical brain regions in PD, PD with dementia (PDD) and DLB, and assessed whether regional differences in synaptic loss are linked to axonal degeneration and neuropathological burden. We included a total of 47 brain donors, 9 PD, 12 PDD, 6 DLB and 20 non-neurological controls. Synaptophysin+ and SV2A+ puncta were quantified in eight cortical regions using a high throughput microscopy approach. Neurofilament light chain (NfL) immunoreactivity, Lewy body (LB) density, phosphorylated-tau and amyloid-ß load were also quantified. Group differences in synaptic density, and associations with neuropathological markers and Clinical Dementia Rating (CDR) scores, were investigated using linear mixed models. We found significantly decreased synaptophysin and SV2A densities in the cortex of PD, PDD and DLB cases compared to controls. Specifically, synaptic density was decreased in cortical regions affected at Braak α-synuclein stage 5 in PD (middle temporal gyrus, anterior cingulate and insula), and was additionally decreased in cortical regions affected at Braak α-synuclein stage 4 in PDD and DLB compared to controls (entorhinal cortex, parahippocampal gyrus and fusiform gyrus). Synaptic loss associated with higher NfL immunoreactivity and LB density. Global synaptophysin loss associated with longer disease duration and higher CDR scores. Synaptic neurodegeneration occurred in temporal, cingulate and insular cortices in PD, as well as in parahippocampal regions in PDD and DLB. In addition, synaptic loss was linked to axonal damage and severe α-synuclein burden. These results, together with the association between synaptic loss and disease progression and cognitive impairment, indicate that regional synaptic loss may underlie clinical differences between PD and PDD/DLB. Our results might provide useful information for the interpretation of synaptic biomarkers in vivo.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Parkinson Disease / Lewy Body Disease / Nervous System Diseases Type of study: Prognostic_studies Limits: Humans Language: En Journal: Acta Neuropathol Commun Year: 2024 Document type: Article Affiliation country: Países Bajos

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Parkinson Disease / Lewy Body Disease / Nervous System Diseases Type of study: Prognostic_studies Limits: Humans Language: En Journal: Acta Neuropathol Commun Year: 2024 Document type: Article Affiliation country: Países Bajos