Clinical application of prion-like seeding in α-synucleinopathies: Early and non-invasive diagnosis and therapeutic development.

The accumulation and deposition of misfolded α-synuclein (α-Syn) aggregates in the brain is the central event in the pathogenesis of α-synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy. Currently, the diagnosis of these diseases mainly relies on the recognition of advanced clinical manifestations. Differential diagnosis among the various α-synucleinopathies subtypes remains challenging. Misfolded α-Syn can template its native counterpart into the same misfolded one within or between cells, behaving as a prion-like seeding. Protein-misfolding cyclic amplification and real-time quaking-induced conversion are ultrasensitive protein amplification assays initially used for the detection of prion diseases. Both assays showed high sensitivity and specificity in detection of α-synucleinopathies even in the pre-clinical stage recently. Herein, we collectively reviewed the prion-like properties of α-Syn and critically assessed the detection techniques of α-Syn-seeding activity. The progress of test tissues, which tend to be less invasive, is presented, particularly nasal swab, which is now widely known owing to the global fight against coronavirus disease 2019. We highlight the clinical application of α-Syn seeding in early and non-invasive diagnosis. Moreover, some promising therapeutic perspectives and clinical trials targeting α-Syn-seeding mechanisms are presented.

Hospital Admissions for Neurodegenerative Diseases during the First Wave of the COVID-19 Pandemic: A Nationwide Cross-Sectional Study from Germany.

(1) Background: The COVID-19 pandemic impacts healthcare utilization across all care settings and health conditions. The objective of this study was to determine changes in hospital admissions for neurodegenerative diseases (NDD) during the first COVID-19 wave in Germany; (2) Methods: This cross-sectional study used nationwide administrative claims data covering 1468 hospitals. The primary outcome was the year-to-year relative change in case numbers during a four-month study period (16 January-15 May 2020 vs. 2019) during the first pandemic wave. Secondary outcomes included year-to-year relative changes during a four-week peak phase (16 March-15 April) and changes between differential phases of the wave. The analyzed NDD comprised progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease; (3) Results: Hospital admissions for any reason decreased by 16.7% in 2020 during the study period and by 36.6% during the peak phase, whereas admissions for NDD decreased by 27.6% and 65.0%, respectively. PSP cases decreased during the study period (-34.7%) and the peak phase (-68.1%) and stayed reduced in a late phase with falling COVID-19 numbers. MSA and ALS cases increased strongest after the peak, with ALS cases being comparatively weakly reduced during the study period (-17.3%) and peak phase (-51.7%); (4) Conclusions: Inpatient care utilization for NDD changed differentially during the first wave of the COVID-19 pandemic in Germany and showed a greater reduction than overall and general neurological admissions. Mitigating long-term health deterioration of this vulnerable subgroup is important to reduce morbidity and mortality in the future.