Evidence map›Paper›PMID 42681667›Full record

SynthesisActa neuropathologica communications2026

A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases.

Leonie Sowoidnich, Aaron L Norman, Florian Gerstner, Josiane K Siemund, Jannik M Buettner, John G Pagiazitis, Vanessa Dreilich, Konstantin Pilz, Dajun Tian, Charlotte J Sumner and 3 more

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Acta neuropathologica communications, 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

5 · Who and what money

Authors and funding

13 authors.

Leonie Sowoidnich *Carl-Ludwig-Institute for Physiology, Leipzig University, 04103, Leipzig, Germany.
Aaron L Norman *Carl-Ludwig-Institute for Physiology, Leipzig University, 04103, Leipzig, Germany.
Florian GerstnerCarl-Ludwig-Institute for Physiology, Leipzig University, 04103, Leipzig, Germany.
Josiane K SiemundCarl-Ludwig-Institute for Physiology, Leipzig University, 04103, Leipzig, Germany.
Jannik M BuettnerCarl-Ludwig-Institute for Physiology, Leipzig University, 04103, Leipzig, Germany.
John G PagiazitisCenter for Motor Neuron Biology and Disease, Columbia University, New York, NY, 10032, USA.
Vanessa DreilichCarl-Ludwig-Institute for Physiology, Leipzig University, 04103, Leipzig, Germany.
Konstantin PilzCarl-Ludwig-Institute for Physiology, Leipzig University, 04103, Leipzig, Germany.
Dajun TianBiogen, Cambridge, MA, 02142, USA.
Charlotte J SumnerDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Angela ParadisBiogen, Cambridge, MA, 02142, USA.
George Z MentisCenter for Motor Neuron Biology and Disease, Columbia University, New York, NY, 10032, USA.
Christian M SimonCarl-Ludwig-Institute for Physiology, Leipzig University, 04103, Leipzig, Germany. christian.simon@medizin.uni-leipzig.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Motor neuron (MN) loss is a hallmark of neurodegenerative disorders, yet its assessment remains variable, confounding mechanistic and therapeutic interpretation. To address this, we conducted a systematic review and meta-analysis of spinal muscular atrophy (SMA) mouse studies, revealing 60% variability in reported MN loss, for which spinal cord sampling emerged as a major contributor. Using a whole-segment approach with tissue clearing, MN tracing, and multimodal imaging, we confirmed segment-dependent differences in MN counts. Common MN markers (SMI-32, Nissl) lacked specificity, whereas choline acetyltransferase (ChAT) provided robust labeling in murine and human spinal cords. Deep learning-based whole-mount segmentation enabled unbiased MN quantification and validated manual counts. Integrating analysis with computational modeling established segment sampling as a key driver of variability and revealed degeneration patterns: widespread MN loss in amyotrophic lateral sclerosis (ALS), selective MN loss in severe SMA, and preservation in mild SMA models. These findings establish a framework for reproducible MN quantification.

Indexed as

Motor NeuronsNeurodegenerative DiseasesSpinal CordAnimalsDisease Models, AnimalHumansMiceMuscular Atrophy, Spinal4-copy SMN2 Type III-like SMAAmyotrophic lateral sclerosisMotor neuron diseasesMotor neuron quantificationNeurodegenerationSMN∆7SOD1-G93ASpinal cordSpinal muscular atrophy

Identifiers

PMID42681667
PMCPMC13536862

What OpenQuestion holds

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Registered trials

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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.