Objective: We have investigated whether alpha-synuclein deposits exists in the brain of patients with Creutzfelt-Jakob disease

Background: Creutzfeldt-Jakob’s disease (CJD) is a prion neurodegenerative disorder that rapidly leads to dementia and death. The fundamental event in the biology of prion diseases is a conformational transition in PrPC to the disease-causing isoform PrPSc. Accumulation of PrPSc leads to its polymerization into amyloid fibrils that consolidate into toxic oligomers and plaques. Brain deposits of pathological protein aggregates also occur in some neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases, in which τ and α-synuclein aggregates have been consistently found, respectively.

Methods: We analyzed the expression of phosphorylated α-synuclein in thirteen cases of sporadic Creutzfeldt-Jakob disease (sCJD) and ten age-matched controls in order to determine the existence and location of pathological protein aggregates. We focused our work on the frontal cortex and cerebellum, since they are specially affected in CJD. Single immunohistochemistry for the previous marker was performed to locate, characterize and understand the pathological protein aggregates.

Results: After carefully analyzing the expression of phosphorylated α-synuclein, we found α-synuclein immunoreactive granular deposits (Lewy dots) in all sCJD brain specimens examined. These inclusions were more prominent in the dentate nucleus and in the cerebellar granular layer than in the frontal cortex, where profuse cytoplasmic inclusions were observed. Surprisingly, we only found Lewy dots and neurites but no Lewy bodies were observed.

Conclusions: The existence of phosphorylated a-synuclein cytoplasmic inclusions and Lewy dots in cases of sCJD disease could suggest a common neurodegenerative pathway between CJD and Parkinson disease, since perturbation of α -synuclein homeostasis is a common mechanism involved in these two pathologies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/presence-of-lewy-dots-in-the-brain-of-patients-with-creutzfeldt-jakob-disease/