Mead S et al. 2026, Genetic causes and modifiers of prion diseases (Lancet Neurol 25(2):181-194, PMID 41579904, doi 10.1016/S1474-4422(25)00451-X)

A narrative review in The Lancet Neurology led by Simon Mead of the MRC Prion Unit at UCL, with co-authors from Goettingen and Bologna, covering inherited prion disease caused by PRNP mutations, the effect of common PRNP variation on sporadic disease, and emerging genetic modifiers outside PRNP. It frames genetics as the basis for early or presymptomatic treatment trials. This record rests on the PubMed, Crossref and Europe PMC records; the full text was not opened.

Key facts

  • Five authors: Simon Mead, Peter Hermann, Tze How Mok, Piero Parchi and Inga Zerr; Mead is the corresponding author.
  • Published in The Lancet Neurology, volume 25, issue 2, pages 181-194, February 2026, DOI 10.1016/S1474-4422(25)00451-X, PMID 41579904.
  • Article type is a review (Europe PMC: Review and Journal Article).
  • Affiliations span the MRC Prion Unit at UCL Institute of Prion Diseases with the National Prion Clinic at UCLH (London), the National Reference Center for CJD Surveillance at Goettingen, and the IRCCS Istituto delle Scienze Neurologiche di Bologna with the University of Bologna.
  • According to the abstract, all inherited prion diseases (genetic CJD, Gerstmann-Straussler-Scheinker disease, fatal familial insomnia) come from PRNP mutations, which partly shape age at onset and clinical features, although presentation can differ widely inside one family.
  • For sporadic disease the abstract says PRNP polymorphisms influence susceptibility, strain selection and progression, and that genes outside PRNP, linked to protein trafficking and lipid metabolism, are emerging as modifiers.
  • The abstract argues that because at-risk people can be identified before symptoms, PrP is a defined drug target and diagnostic biomarkers are emerging, the field is well placed for early, disease-modifying treatment.
  • The scout's citation details (journal, volume, pages, PMID, DOI) were confirmed. The scout listed only the first author; the record has five authors.

Timeline

  1. 2026Crossref created the DOI record for the article (22 January); this is a registration date, not necessarily an online publication date.
  2. 2026Article appears in Lancet Neurology 25(2), pages 181-194 (Europe PMC first publication date 1 February).

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Last checked 1 November 2026

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