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Abstract
Background MRI is an important tool for disease diagnosis of Creutzfeldt-Jakob disease (CJD), yet its role in identifying preclinical stages of disease remains unclear. Here, we explored subtle white matter (WM) alterations in genetic CJD (gCJD) patients and in asymptomatic E200K mutation carriers using MRI, depending on total tau protein (t-tau) levels in CSF.
Methods Six symptomatic gCJD patients and N=60 healthy relatives of gCJD patients were included. Participants underwent genetic testing for the E200K mutation, MRI scans at 3T and a lumbar puncture (LP) for t-tau. Diffusion tensor imaging (DTI) metrics were calculated along WM tracts.
Results gCJD patients demonstrated higher mean diffusivity (MD), radial diffusivity (RD) and lower fractional anisotropy (FA) values compared with healthy relatives in several WM tracts (p<0.05). Out of the healthy relatives, 50% (N=30) were found to be carriers of the E200K mutation. T-tau levels in cerebrospinal fluid (CSF) were above the normal range (>290 pg/mL) in N=8 out of 23 carriers who underwent an LP. No significant differences in FA, MD, axial diffusivity (AD) and RD were detected between healthy mutation carriers (HMC) and healthy non-carriers within the WM tracts. Finally, significantly higher FA and lower MD, RD and AD along several WM tracts were found in HMC with elevated t-tau compared with HMC with normal t-tau (p<0.05).
Conclusions DTI abnormalities along WM tracts were found in healthy E200K mutation carriers with elevated t-tau in CSF. Longer follow-up is required to determine whether these subtle WM alterations are predictive of future conversion to symptomatic gCJD.
Trial registration number NCT05746715.
- CREUTZFELDT-JAKOB DISEASE
- MRI
- GENETICS
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Footnotes
X @DrobyAmgad
NO and AD contributed equally.
Contributors NO: writing–review and editing, writing–original draft, methodology, investigation, formal analysis, data curation, conceptualisation. AD: writing–review and editing, writing–original draft, methodology, investigation, formal analysis, data curation, conceptualisation. RS: data curation and analysis. NT: data curation. ABD: data curation. TS: writing–review and editing. YA: data analysis. RA: writing–review and editing. TN: writing–review and editing. AT: writing
–review and editing. AM: writing–review and editing. MGW: data curation and analysis. OG: Data curation and analysis. TG: Data curation and analysis. AO-U: data curation and analysis. NG: writing–review and editing. NB: writing–review and editing, writing–original draft, methodology, investigation, formal analysis, data curation, conceptualisation.
Funding This study was funded by Ionis Pharmaceuticals. The authors wish to thank the study participants for their contribution and devotion.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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