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European Journal of Neurology

Plasma Proteomic Changes in GRN and C9orf72 Frontotemporal Dementia

  • July 12, 2026
  • Nicholas Ashton, et al., Banner Sun Health
Product:
CNS Disease Panel 120
Topic:
CNS
Disease Area:
Frontal Temporal Dementia (FTD)
Sample Type:
Plasma
Back to Publications​
  • July 12, 2026
Product:
CNS Disease Panel 120
Topic:
CNS
Disease Area:
Frontal Temporal Dementia (FTD)
Sample Type:
Plasma

Abstract

Background

Biomarkers 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.

Methods

We 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.

Results

In 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.

Conclusions

Using 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.

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Authors and Affiliations

Joel Simrén1,2 | Andrea L. Benedet1 | Guglielmo Di Molfetta1 | Ilaria Pola1 | Kübra Tan1 | Valentina Cantoni3 | Ilenia Libri3 | Jasmine Rivolta3 | Roberta Ghidoni4 | Henrik Zetterberg1,2,5,6,7,8 | Barbara Borroni3,4 | Nicholas J. Ashton1,9,10,11

1 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden |

2 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden |

3 Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy |

4 Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy |

5 Department of Neurodegenerative Disease, Institute of Neurology, UCL, London, UK |

6 UK Dementia Research Institute, UCL, London, UK |

7 Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China |

8 Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA |

9 Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK |

10 Banner Alzheimer’s Institute, Phoenix, Arizona, USA |

11 Banner Sun Health Research Institute, Sun City, Arizona, USA

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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.