Genetic Creutzfeldt Jakob disease: Can MRI serve as an early diagnostic biomarker?. (1st February 2022)

• Record Type: Journal Article
• Authors: Omer, Nurit; Silbak, Rawan; Trabulus, Noa; Gana‐Weisz, Mali; Goldstein, Orly; Glinka, Tal; Orr‐Urterger, Avi; Giladi, Nir; Droby, Amgad; Bregman, Noa
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.057783
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Genetic CJD (gCJD) is a rare prion disease, with a large cluster in Jews of Libyan origin. The disease is caused by an E200K mutation in the PRNP gene, and is inherited in an autosomal dominant manner with penetrance approaching 100% throughout life. While the mutation is inborn, symptoms usually appear in late adulthood, leading to a rapid neurological deterioration until death. Characterization of a prodromal stage is crucial for understanding the processes leading to disease onset, and eventually for defining the right timing for disease modifying treatment, when available. Objective: To investigate early MRI candidate markers in asymptomatic E200K carriers based on diffusion tensor imaging (DTI). Method: 51 participants (>49 years old) first degree relatives of gCJD patients were enrolled. All participants underwent genetic sequencing and an MRI scan at 3T acquiring DTI datasets. Tract Based Spatial Statistics (TBSS) was performed for DTI. Result: E200K mutation was detected in 24 participants (55.8+−6.25, F:M 13:11). Based on TBSS, reduced fractional anisotropy was detected in the anterior limb of internal capsule, the superior fronto‐occipital fasciculus, thalamus and anterior thalamic radiation, and ventromedial prefrontal cortex when compared to non‐carriers (p=0.001 uncorrected). However, these between group differences did not survive correction for multiple comparisons (FDR). Conclusion: Based on the obtained results, only subtle white matter differences can be detected between carriers and non‐carriers of E200K. A longitudinal study design with a larger sample size is warranted in order to characterize the evolution of underlying pathophysiological processes prior to phenoconversion