Evidence map›Paper›PMID 39934841›Full record

ArticleActa neuropathologica communications2025

Neuropathological stages of neuronal, astrocytic and oligodendrocytic alpha-synuclein pathology in Parkinson's disease.

Maria Otero-Jimenez, Marcelina J Wojewska, Lawrence P Binding, Simona Jogaudaite, Sandra Gray-Rodriguez, Alexandra L Young, Steve Gentleman, Javier Alegre-Abarrategui

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In one paragraph

Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

  1. Review
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  4. Where do PDD and DLB SYNdromes fit in neuronal alpha-SYNuclein biological frameworks?Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Maria Otero-JimenezDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Marcelina J WojewskaDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Lawrence P BindingDepartment of Computer Science, UCL Hawkes Institute, University College London, London, UK.
Simona JogaudaiteDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Sandra Gray-RodriguezDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Alexandra L YoungDepartment of Computer Science, UCL Hawkes Institute, University College London, London, UK.
Steve GentlemanDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Javier Alegre-AbarrateguiDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK. j.alegre@imperial.ac.uk.

Funding

Wellcome TrustWellcome Trust 227341/Z/23/Z
6 · The paper itself

Abstract

Alpha-synucleinopathies are neurodegenerative diseases characterized by the spread of alpha-synuclein (α-syn) aggregates throughout the central nervous system in a stereotypical manner. These diseases include Lewy body disease (LBD), which encompass Dementia with Lewy bodies (DLB), Parkinson's Disease (PD), and Parkinson's Disease Dementia (PDD), and Multiple System Atrophy (MSA). LBD and MSA chiefly contain α-syn aggregates in neurons and oligodendrocytes, respectively, although glial α-syn pathology in LBD is increasingly being recognized. Semi-quantitative and machine learning-based quantifications of neuronal, oligodendrocytic and astrocytic α-syn pathology were implemented on a cohort of LBD and MSA post-mortem tissue samples. The neuroanatomical distribution of each cell-type specific α-syn pathology was evaluated using conditional probability matrices and Subtype and Stage Inference (SuStaIn) algorithm. We revealed extensive glial α-syn pathology in LBD, emphasizing the disease- and region-specific profile of astrocytic α-syn pathology, which was absent in MSA and minimal in the substantia nigra of LBD. Furthermore, we have described distinct morphologies of astrocytic α-syn pathology, which were found to correlate with the density of astrocytic α-syn inclusions. Astrocytic α-syn pathology was mainly centered in the amygdala and exhibited a unique stereotypical progression whilst oligodendrocytes displayed a distribution akin to the established neuronal progression pattern. SuStaIn modeling was further used to test for heterogeneity in the spatiotemporal progression, revealing that a subset of cases might follow an alternative pattern. Based on these findings, we introduce a novel multimodal progression framework that integrates, for the first time, the temporal and spatial progression of astrocytic and oligodendrocytic α-syn pathology alongside neuronal pathology in PD, providing further information regarding the role of neurons and glia in disease pathogenesis.

Indexed as

alpha-SynucleinAstrocytesBrainNeuronsOligodendrogliaParkinson DiseaseAgedAged, 80 and overFemaleHumansLewy Body DiseaseMaleMiddle AgedMultiple System Atrophyalpha-SynucleinAlpha-synucleinAlpha-synucleinopathiesAstrocytesNeuroanatomical distributionParkinson’s diseaseStaging

Identifiers

PMID39934841
PMCPMC11816504

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.