Seed amplification assay of nasal swab extracts for accurate and non-invasive molecular diagnosis of neurodegenerative diseases

Suying Duan, Jing Yang, Zheqing Cui, Jiaqi Li, Honglin Zheng, Taiqi Zhao, Yanpeng Yuan, Yutao Liu, Lu Zhao, Yangyang Wang, Haiyang Luo, Yuming Xu

Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx. Dysosmia is regarded as an early sign of coronavirus disease 2019 (COVID-19), and nasal swabs are the gold standard for the detection. By nasal swabs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling. Similarly, olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. In neurodegenerative diseases, nasal swab tests are currently being explored using seed amplification assay (SAA) of pathogenic misfolded proteins, such as prion, α-synuclein, and tau. These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner. SAA for misfolded prion-like proteins from nasal swab extracts has been developed, conceptually analogous to PCR, showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage. Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease.