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dc.contributor.authorColom-Cadena, Martí
dc.contributor.authorPegueroles, Jordi
dc.contributor.authorHerrmann, Abigail G.
dc.contributor.authorHenstridge, Christopher M.
dc.contributor.authorMuñoz, Laia
dc.contributor.authorQuerol-Vilaseca, Marta
dc.contributor.authorSan Martin, Carla
dc.contributor.authorLuque-Cabecerans, Joan
dc.contributor.authorClarimon, Jordi
dc.contributor.authorBelbin, Olivia
dc.contributor.authorNuñez-Llaves, Raúl
dc.contributor.authorBlesa, Rafael
dc.contributor.authorSmith, Colin
dc.contributor.authorMcKenzie, Chris-Anne
dc.contributor.authorFrosch, Matthew P.
dc.contributor.authorRoe, Allyson
dc.contributor.authorFortea, Juan
dc.contributor.authorAndilla, Jordi
dc.contributor.authorLoza-Alvarez, Pablo
dc.contributor.authorGelpi, Ellen
dc.contributor.authorHyman, Bradley T.
dc.contributor.authorSpires-Jone, Tara L.
dc.contributor.authorLleó, Alberto
dc.contributor.otherUniversitat Politècnica de Catalunya. Institut de Ciències Fotòniques
dc.date.accessioned2017-12-11T16:49:11Z
dc.date.available2018-05-01T00:30:29Z
dc.date.issued2017-11-23
dc.identifier.citationColom-Cadena, M. [et al.]. Synaptic phosphorylated a-synuclein in dementia with Lewy bodies. "", 23 Novembre 2017, vol. 140, núm. 12, p. 3204-3214.
dc.identifier.issn0006-8950
dc.identifier.urihttp://hdl.handle.net/2117/111726
dc.description.abstractDementia with Lewy bodies is characterized by the accumulation of Lewy bodies and Lewy neurites in the CNS, both of which are composed mainly of aggregated a-synuclein phosphorylated at Ser129. Although phosphorylated a-synuclein is believed to exert toxic effects at the synapse in dementia with Lewy bodies and other a-synucleinopathies, direct evidence for the precise synaptic localization has been difficult to achieve due to the lack of adequate optical microscopic resolution to study human synapses. In the present study we applied array tomography, a microscopy technique that combines ultrathin sectioning of tissue with immunofluorescence allowing precise identification of small structures, to quantitatively investigate the synaptic phosphorylated a-synuclein pathology in dementia with Lewy bodies. We performed array tomography on human brain samples from five patients with dementia with Lewy bodies, five patients with Alzheimer’s disease and five healthy control subjects to analyse the presence of phosphorylated a-synuclein immunoreactivity at the synapse and their relationship with synapse size. Main analyses were performed in blocks from cingulate cortex and confirmed in blocks from the striatum of cases with dementia with Lewy bodies. A total of 1 318 700 single pre- or post-synaptic terminals were analysed. We found that phosphorylated a-synuclein is present exclusively in dementia with Lewy bodies cases, where it can be identified in the form of Lewy bodies, Lewy neurites and small aggregates (50.16 mm3). Between 19% and 25% of phosphorylated a-synuclein deposits were found in presynaptic terminals mainly in the form of small aggregates. Synaptic terminals that co-localized with small aggregates of phosphorylated a-synuclein were significantly larger than those that did not. Finally, a gradient of phosphorylated a-synuclein aggregation in synapses (pre4pre + post4post-synaptic) was observed. These results indicate that phosphorylated a-synuclein is found at the presynaptic terminals of dementia with Lewy bodies cases mainly in the form of small phosphorylated a-synuclein aggregates that are associated with changes in synaptic morphology. Overall, our data support the notion that pathological phosphorylated a-synuclein may disrupt the structure and function of the synapse in dementia with Lewy bodies.
dc.format.extent11 p.
dc.language.isoeng
dc.publisherOxford
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Spain
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subjectÀrees temàtiques de la UPC::Física
dc.subject.lcshDementia
dc.subject.otherdementia
dc.titleSynaptic phosphorylated a-synuclein in dementia with Lewy bodies
dc.typeArticle
dc.subject.lemacDemència
dc.description.peerreviewedPeer Reviewed
dc.relation.publisherversionhttps://academic.oup.com/brain/article-abstract/140/12/3204/4643006?redirectedFrom=PDF
dc.rights.accessOpen Access
dc.description.versionPostprint (author's final draft)
dc.relation.projectidinfo:eu-repo/grantAgreement/MINECO//SEV-2015-0522/ES/AGR-INSTITUTO DE CIENCIAS FOTONICAS/
local.citation.volume140
local.citation.number12
local.citation.startingPage3204
local.citation.endingPage3214


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