Author Interviews, Dermatology, JAMA, Parkinson's / 01.10.2020 Interview with: Wenquan Zou, MD/PhD, Professor Department of Pathology Associate Director National Prion Disease Pathology Surveillance Center Case Western Reserve University School of Medicine Cleveland, Ohio 44106 What is the background for this study? Response: Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. It is characterized by the accumulation of pathologically misfolded α-synuclein (αSynP) aggregates in the brain. Currently, a definite diagnosis relies on the detection of αSynP-containing Lewy bodies in the brain of PD patients. Development of a reliable and sensitive assay for αSynP in easily accessible peripheral tissue specimens is critical for early or differential diagnosis, determination of disease severity, and evaluation of therapeutic efficacy in clinical trials. Previous studies have revealed that the pathologically phosphorylated α-synuclein is detectable with traditional immunohistochemistry (IHC) and immunofluorescence (IF) microscopy but the sensitivity with IHC/IF is highly variable and inconsistent. Also the prion-like aggregation seeding activity of αSynP is detected in cerebrospinal fluid (CSF) of Parkinson’s disease patients with highly sensitive real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification assays (PMCA). But the lumbar puncture to collect CSF is more invasive compared to skin punch biopsy. (more…)
Author Interviews / 23.01.2019 Interview with: Byron Caughey, Ph.D.  Senior Investigator Chief, TSE/prion Biochemistry Section Laboratory of Persistent Viral Diseases NIH/NIAID Rocky Mountain Laboratories . Hamilton, MT 59840 USA What is the background for this study? Would you briefly explain the significance of prion-induced diseases and why they have been difficult to diagnosis?  Response: Although prion diseases such as Creutzfeldt-Jakob disease (CJD) are rarer than many other neurodegenerative diseases in humans, they are rapidly fatal, untreatable and transmissible. Therefore it is important to be able to diagnose prion diseases as early as possible, not only to accurately inform patients, families and caregivers, but also to reduce risks of transmission and  improve prospects for developing therapeutics. Toward these goals, we have shown that our RT-QuIC prion seed amplification assays are highly accurate for diagnosing sporadic CJD using patients’ spinal fluid and/or nasal brushings in the clinical phase of disease. However, these particular specimens may not always be available, and it remains unclear how early they become RT-QuIC-positive in infected individuals in the months or years prior to the onset of overt clinical signs. We also showed recently that skin samples obtained post-mortem from sCJD patients are RT-QuIC positive. In the current study, we determined how early prion seeds appear in the rodents infected with prions in order to gain clues as to whether analyses of skin biopsies might provide a means of early preclinical detection of prion infections in humans. (more…)