Evidence map›Paper›PMID 41618337›Full record

ArticleTranslational neurodegeneration2026

Mapping cellular vulnerability in Parkinson's disease using retro-AAVs and preformed α-synuclein fibrils.

Fanni F Geibl, Ahmed A S Musa, Leo Dietrich, Helena Wolter, David L Wokosin, Sharof Khudayberdiev, Marco B Rust, Rong Chen, Valina L Dawson, Ted M Dawson and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational neurodegeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

13 authors.

Fanni F GeiblDepartment of Psychiatry and Psychotherapy, Marburg University, Rudolf-Bultmann-Str. 8, 35043, Marburg, Germany.ORCID http://orcid.org/0000-0002-5480-0463
Ahmed A S MusaDepartment of Psychiatry and Psychotherapy, Marburg University, Rudolf-Bultmann-Str. 8, 35043, Marburg, Germany.
Leo DietrichDepartment of Psychiatry and Psychotherapy, Marburg University, Rudolf-Bultmann-Str. 8, 35043, Marburg, Germany.
Helena WolterDepartment of Psychiatry and Psychotherapy, Marburg University, Rudolf-Bultmann-Str. 8, 35043, Marburg, Germany.
David L WokosinDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Sharof KhudayberdievMolecular Neurobiology Group, Institute of Physiological Chemistry, Marburg University, 35032, Marburg, Germany.ORCID http://orcid.org/0000-0003-0349-116X
Marco B RustMolecular Neurobiology Group, Institute of Physiological Chemistry, Marburg University, 35032, Marburg, Germany.ORCID http://orcid.org/0000-0003-2737-1250
Rong ChenNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.ORCID http://orcid.org/0000-0002-2915-3970
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.ORCID http://orcid.org/0000-0002-6459-0893
Wolfgang H OertelDepartment of Neurology, Marburg University, 35043, Marburg, Germany.ORCID http://orcid.org/0000-0002-7582-8166
D James SurmeierDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.ORCID http://orcid.org/0000-0002-6376-5225
Martin T HenrichDepartment of Psychiatry and Psychotherapy, Marburg University, Rudolf-Bultmann-Str. 8, 35043, Marburg, Germany. martin.henrich@uni-marburg.de.ORCID http://orcid.org/0000-0001-8295-4884

Funding

Alzheimer Forschung Initiative 22003Deutsche Forschungsgemeinschaft RU1232/10-1Philipps-Universität Marburg SUCCESS Program
6 · The paper itself

Abstract

backgroundParkinson disease (PD) is characterized by progressive neuronal loss within defined brain regions, accompanied by α-synuclein (αSyn)-rich inclusions, termed Lewy pathology (LP). However, it is unclear which cellular factors render certain neuronal populations vulnerable, while others stay devoid of LP throughout the course of disease.

methodsThis study aimed to identify and compare the cellular architecture of vulnerable and non-vulnerable neurons exposed to αSyn pathology by using a projection-based retro-AAV approach in combination with an in vivo α-synucleinopathy mouse model. To do so, a set of viral genetic, immunohistochemical, and optical tools was used in combination with the preformed αSyn fibril (PFF) model.

resultsαSyn pathology propagated robustly into the input connectome of the pedunculopontine nucleus (PPN). However, we observed a marked mismatch between the anatomically expected and the actual distribution of pathology. While anatomically connected neurons in the bed nucleus of the stria terminalis (BST) and the central amygdala (CEA) accumulated substantial αSyn pathology, equally strong connected neurons of the substantia nigra pars reticulata (SNr), and the dentate nucleus (DN) were devoid of pathology. Second, cellular vulnerability and resilience were consistent and reproducible features. When PFFs were injected into alternative major output projection sites of BST, CEA, SNr, and DN, we observed similar patterns of αSyn accumulation. Third, projection-specific axonal mapping revealed that the αSyn-accumulating BST and CEA neurons possessed larger axonal arbors than the more resilient neurons in SNr and DN. Correspondingly, neurons in BST and CEA exhibited higher basal mitochondrial oxidation levels, indicating an increased bioenergetic burden. Finally, the site of initial seeding significantly influenced the extent of developing brain-wide pathology, suggesting that certain brain regions may function as "super-seeders", promoting widespread propagation of pathology, while others contribute relatively little to the global LP burden.

conclusionsαSyn pathology propagates along anatomical pathways, but cell-autonomous factors determine if a neuron exposed to misfolded αSyn will develop Lewy-like pathology or not.

Indexed as

alpha-SynucleinBrainNeuronsParkinson DiseaseAnimalsDisease Models, AnimalHumansLewy BodiesMiceMice, Transgenicalpha-SynucleinLewy pathologyOxidative stressParkinson’s diseasePreformed αSyn fibrilRetro-AAVsα-Synuclein

Identifiers

PMID41618337
PMCPMC12859986

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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.