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Lewy bodies are not associated with neuronal or synaptic loss in dementia with lewy bodies

2026-06Artigo científico Acesso aberto
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datacite.subject.sdg03:Saúde de Qualidade
datacite.subject.sdg09:Indústria, Inovação e Infraestruturas
datacite.subject.sdg04:Educação de Qualidade
dc.contributor.authorHawksworth, Jade I.
dc.contributor.authorKirkby‐Geddes, Eddie
dc.contributor.authorThom, Searlait
dc.contributor.authorO'Neill, Joe
dc.contributor.authorIkwue, Amelia
dc.contributor.authorWood, Lucy
dc.contributor.authorOuteiro, Tiago
dc.contributor.authorErskine, Daniel
dc.date.accessioned2026-07-01T14:11:38Z
dc.date.available2026-07-01T14:11:38Z
dc.date.issued2026-06
dc.description.abstractAims: The misfolding and accumulation of the protein α-synuclein (αSyn) into cytoplasmic inclusions termed Lewy bodies (LBs) and Lewy neurites is the defining neuropathological feature of LB diseases, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The loss of neurons and/or synapses has been postulated to underlie the clinical syndrome of DLB. The present study sought to elucidate the relationship between LB burden and neuronal and synaptic loss in DLB. Methods: Post-mortem brain tissue from the cingulate gyrus and inferior temporal gyrus, two regions vulnerable to LB pathology, was obtained from DLB (N=20) and control cases (N=20). Formalin-fixed paraffin-embedded tissue was stained to quantify LB, Alzheimer-type pathology and a neuronal marker. Frozen tissue from the contralateral hemisphere was processed for immunoblotting to compare the abundance of synaptic markers across cases. Results: Across both regions, no evidence of reduced total neuronal density was observed, but a modest reduction in parvalbumin interneurons was observed in the cingulate gyrus, and there were only modest reductions in some synaptic markers in DLB. LB burden was markedly variable across DLB cases but was not associated with any synaptic marker abundance or neuronal density. Conclusions: Taken together, these findings do not support an association between LB density and neuronal or synaptic loss in DLB, even in regions with particularly high burdens of LBs, such as the cingulate gyrus. These findings suggest that the link between αSyn proteinopathy and disease requires further investigation.eng
dc.description.sponsorshipARUKSRF2022A-006
dc.identifier.doi10.1111/nan.70085
dc.identifier.eissn1365-2990
dc.identifier.issn0305-1846
dc.identifier.urihttp://hdl.handle.net/10400.1/29188
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWiley
dc.relation.ispartofNeuropathology and Applied Neurobiology
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAlpha-synuclein
dc.subjectDementia with Lewy bodies
dc.subjectHistopathology
dc.subjectNeuronal density
dc.subjectSynaptic proteins
dc.titleLewy bodies are not associated with neuronal or synaptic loss in dementia with lewy bodieseng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue3
oaire.citation.startPagee70085
oaire.citation.titleNeuropathology and Applied Neurobiology
oaire.citation.volume52
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameOuteiro
person.givenNameTiago
person.identifier.orcid0000-0003-1679-1727
relation.isAuthorOfPublicationc93b0b78-4cd4-40ac-adfb-32fdf38fec06
relation.isAuthorOfPublication.latestForDiscoveryc93b0b78-4cd4-40ac-adfb-32fdf38fec06

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