Variably Protease‐Sensitive Prionopathy: Two New Cases With Motor Neuron‐Dementia Syndrome

We describe two patients with variably protease-sensitive prionopathy (VPSPr) who developed progressive upper motor neuron symptoms, insomnia, behavioral and cognitive decline, compatible with primary lateral sclerosis associated with frontotemporal dementia (FTD). Neuropathology revealed a spongiform encephalopathy with frontotemporal and pronounced thalamic involvement, associated with fine synaptic abnormal prion protein conformer (PrP<sup>Sc</sup>) deposits, microplaques, and intraneuronal aggregates. Western blot analysis revealed a characteristic VPSPr proteolytic profile, lacking the diglycosylated band. Both patients were methionine homozygous at PRNP codon 129 and carried no pathogenic mutations. These cases illustrate that VPSPr can present with a prominent motor neuron syndrome and FTD features.

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Publication Details

Journal
Annals of Clinical and Translational Neurology
Published
2025-12-27
DOI
https://doi.org/10.1002/acn3.70294
Primary Topic
Prion Diseases and Protein Misfolding
Type
article
Field-Weighted Citation Impact
0.00

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article

Variably Protease‐Sensitive Prionopathy: Two New Cases With Motor Neuron‐Dementia Syndrome

I. N. Ferrer, María Elena Erro, Ivonne Jericó, Hasier Eraña et al.
Annals of Clinical and Translational Neurology
Prion Diseases and Protein Misfolding
article

Variably Protease‐Sensitive Prionopathy: Two New Cases With Motor Neuron‐Dementia Syndrome

I. N. Ferrer, María Elena Erro, Ivonne Jericó, Hasier Eraña, Javier Sanchez Ruiz de Gordoa, María Cristina Caballero, María Victoria Zelaya, Anika Simonovska‐Serra, Joaquín Castilla, Ellen Gelpi, Fermín García‐Amigot
article en

Abstract

We describe two patients with variably protease-sensitive prionopathy (VPSPr) who developed progressive upper motor neuron symptoms, insomnia, behavioral and cognitive decline, compatible with primary lateral sclerosis associated with frontotemporal dementia (FTD). Neuropathology revealed a spongiform encephalopathy with frontotemporal and pronounced thalamic involvement, associated with fine synaptic abnormal prion protein conformer (PrP<sup>Sc</sup>) deposits, microplaques, and intraneuronal aggregates. Western blot analysis revealed a characteristic VPSPr proteolytic profile, lacking the diglycosylated band. Both patients were methionine homozygous at PRNP codon 129 and carried no pathogenic mutations. These cases illustrate that VPSPr can present with a prominent motor neuron syndrome and FTD features.

Annals of Clinical and Translational Neurology
Ikerbasque (ES), Instituto de Salud Carlos III (ES), Bellvitge University Hospital (ES), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Comprehensive Cancer Center Vienna (AT), Complejo Hospitalario de Navarra (ES), CIC bioGUNE (ES), Centro de Investigación Biomédica en Red (ES), Navarrabiomed (ES), Light Prescriptions Innovators (Spain) (ES), Medical University of Vienna (AT), Universidad de Navarra (ES)
European Commission, Ministerio de Ciencia e Innovación, European Regional Development Fund, Agencia Estatal de Investigación, Interreg
Openalex Percentile: Top 36%
Prion Diseases and Protein Misfolding
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