Evidence mapPaperPMID 42438357Full record

ArticleEuropean journal of neurology2026

Plasma Proteomic Changes in GRN and C9orf72 Frontotemporal Dementia.

Joel Simrén, Andrea L Benedet, Guglielmo Di Molfetta, Ilaria Pola, Kübra Tan, Valentina Cantoni, Ilenia Libri, Jasmine Rivolta, Roberta Ghidoni, Henrik Zetterberg and 2 more

Abstract read
In one paragraph

Article in European journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

12 authors.

Joel SimrénDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Andrea L BenedetDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Guglielmo Di MolfettaDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Ilaria PolaDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Kübra TanDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Valentina CantoniDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Ilenia LibriDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Jasmine RivoltaDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Roberta GhidoniMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.ORCID https://orcid.org/0000-0002-7691-1957
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Barbara BorroniDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

Funding

Beiglers stiftelseBluefield ProjectStiftelsen för Gamla Tjänarinnor
6 · The paper itself

Abstract

backgroundBiomarkers reflecting the complex pathophysiology of genetic frontotemporal dementia (FTD) will be increasingly important with the advent of therapeutic trials aiming to slow or prevent the disease. In this study, we aimed to identify blood biomarker candidates using a multiplex panel of CNS-related proteins.

methodsWe cross-sectionally evaluated 67 carriers (21 presymptomatic and 46 symptomatic) of pathogenic FTD-causing mutations in the GRN (n = 30 symptomatic) and C9orf72 (n = 16 symptomatic) genes and 42 matched non-carriers. Clinical severity was estimated using the CDR Dementia Staging Instrument with National Alzheimer Coordinating Centre Frontotemporal Lobar Degeneration component (CDR plus NACC FTLD). A total of 124 CNS-related proteins were measured in plasma using the NUcleic acid Linked Immuno-Sandwich Assay (NULISA) CNS panel. Group-level changes were then investigated using linear and non-linear regression models.

resultsIn GRN- and C9orf72-FTD, neurofilament light (NfL) was the most clearly altered protein compared with non-carriers (GRN: β [95% CI] = 4.0 standard deviations [3.6-4.4], C9orf72: β = 2.8 [2.2-3.4]), followed by neurofilament heavy (NfH; GRN: β = 0.83 [0.39-1.3], C9orf72: β = 1.4 [0.8-2.0]). Proteins exclusively altered in GRN-FTD included glial fibrillary acidic protein (GFAp; β = 0.50 [0.20-0.81]) and vascular cell adhesion protein 1 (VCAM1; Standardized β = -0.90 [-1.4 to -0.38]), changing with increasing disease severity. Neuronal pentraxin receptor (NPTXR; β = -0.94 [-1.5 to -0.4]) was selectively reduced in C9orf72-FTD. Nominally changed proteins in C9orf72-FTD included several inflammatory mediators.

conclusionsUsing this multiplex panel, established markers recapitulated previously established trends, while less-studied biomarker candidates were also identified. If validated in independent cohorts, these candidates could broaden the repertoire of blood biomarkers reflecting genetic FTD pathophysiology.

Indexed as

C9orf72 ProteinFrontotemporal DementiaProgranulinsAgedBiomarkersCross-Sectional StudiesFemaleHumansMaleMiddle AgedNeurofilament ProteinsProteomicsBiomarkersC9orf72 ProteinC9orf72 protein, humanGRN protein, humanneurofilament protein LNeurofilament ProteinsProgranulinsbiomarkersfrontotemporal dementiaproteomics

Identifiers

PMID42438357
PMCPMC13358372

What Socratic 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 Socratic graph.