Search

Background and Purpose: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease caused by an abnormal isoform of the human prion protein. Structural magnetic resonance imaging in patients with pathologically confirmed sCJD was compared with cognitively normal individuals to identify a cortical thickness signature of sCJD., Methods: This retrospective cross-sectional study compared patients with autopsy-confirmed sCJD with dementia (n = 11) with age- and sex-matched cognitively normal individuals (n = 22). We identified regions of interest (ROIs) in which cortical thickness was most affected by sCJD. Within patients with sCJD, the relationship between ROI cortical thickness and clinical measures (disease duration, cerebrospinal fluid tau and diffusion-weighted imaging abnormalities) was evaluated., Results: Compared with cognitively normal individuals, patients with sCJD had significantly reduced cortical thickness in multiple ROIs, including the fusiform gyrus, precentral gyrus, precuneus and superior temporal gyrus bilaterally; the caudal middle frontal gyrus, superior frontal gyrus, postcentral gyrus, inferior temporal gyrus and transverse temporal gyrus in the left hemisphere; and the superior parietal lobule in the right hemisphere. Only one patient with sCJD had co-pathology consistent with Alzheimer's disease. Reduced cortical thickness did not correlate with disease duration, presence of diffusion restriction or elevated cerebrospinal fluid tau., Conclusion: Cortical signature changes in sCJD may reflect brain changes not captured by standard clinical measures. This information may be used with clinical measures to inform the progression of sCJD and patterns of prion protein spread throughout the brain. These results may have implications for prediction of symptomatic progression and plausibly for development of therapeutic strategies., (© 2019 EAN.)

Objective: To determine whether specific patterns of [ 18 F]-AV-1451 tau-PET retention are observed in patients with autopsy-proven sporadic Creutzfeldt-Jakob disease (CJD)., Methods: In vivo [ 18 F]-AV-1451 PET neuroimaging was performed in 5 patients with sporadic CJD (median age, 66 years [63-74]), and results were compared to cognitively normal (CN) persons (n = 44; median age, 68 years [63-74]) and to participants with very mild Alzheimer disease (AD) dementia (n = 8; median age, 77 years [63-90]). Autopsy was completed in all patients with CJD, confirming the clinical diagnosis and permitting characterization of AD neuropathologic change (ADNC)., Results: All patients with CJD presented with rapidly progressive dementia, typical magnetic resonance brain imaging changes, and elevated CSF total tau (median = 6,519; range = 1,528-13,240 pg/mL). Death occurred within 9 months of symptom onset, with a median 1 month (0.2-3.3) interval from [ 18 F]-AV-1451 PET to autopsy. No unique pattern of [ 18 F]-AV-1451 retention was observed on visual inspection. Summary standardized uptake value ratios in patients with CJD (1.17, 1.08-1.36) were indistinguishable from CN persons (1.14, 0.84-1.54; p = 0.6), and well below those of participants with AD (2.23, 1.60-3.04; p ≤ 0.01). [ 18 F]-AV-1451 retention in patients with CJD and CN persons was similar in brain areas frequently affected in AD and CJD. Neuropathologic analysis confirmed the clinical diagnosis in all patients with CJD. Four patients with CJD also had low-level ADNC (A1B1C0); one patient had intermediate-level ADNC (A2B2C1/2)., Conclusion: Increased [ 18 F]-AV-1451 retention was not observed in patients with rapidly progressive dementia due to sporadic CJD. The [ 18 F]-AV-1451 PET tracer maintains good specificity for paired helical tau filaments associated with AD dementia., (© 2018 American Academy of Neurology.)

Background: Dominantly inherited Creutzfeldt-Jakob disease (CJD) represents 5% to 15% of all CJD cases. The E200K mutation in the prion protein (PrP) gene (PRNP) is the most frequent cause of familial CJD. Coexistent amyloid beta (Abeta) plaques have been reported in some transmissible spongiform encephalopathies but to date have not been reported in familial CJD with the E200K mutation., Objective: To characterize a family with CJD in which Abeta plaques codistribute with spongiform degeneration., Design: Clinicopathologic and molecular study of a family with CJD with the E200K-129M haplotype., Setting: Alzheimer disease research center., Participants: Two generations of a family., Main Outcome Measures: Clinical, biochemical, and neuropathologic observations in 2 generations of a family., Results: In this kindred, 3 autopsied cases showed pathologic changes typical for the E200K-129M haplotype, including spongiform degeneration, gliosis, neuronal loss, and PrP deposition. Moreover, 2 of these cases (ages 57 and 63 years) showed numerous Abeta plaques codistributed with spongiform degeneration. APOE genotyping in 2 cases revealed that Abeta plaques were present in the APOE epsilon4 carrier but not in the APOE epsilon4 noncarrier. Two additional cases exhibited incomplete penetrance, as they had no clinical evidence of CJD at death after age 80 years but had affected siblings and children., Conclusions: To our knowledge, this is the first description of Abeta plaques in familial CJD with the E200K mutation. The codistribution of plaques and CJD-associated changes suggests that PrP plays a central role in Abeta formation and that Abeta pathology and prion disease likely in fluence each other. The kindred described herein provides support that PrP(E200K) may result in increased Abeta deposition.