Performance of αSynuclein RT-QuIC in relation to neuropathological staging of Lewy body disease
Year: 2022
Type: article
Study design: Observational Study
Abstract: Currently, there is a need for diagnostic markers in Lewy body disorders (LBD). α-synuclein (αSyn) RT-QuIC has emerged as a promising assay to detect misfolded αSyn in clinically or neuropathologically established patients with various synucleinopathies. In this study, αSyn RT-QuIC was used to analyze lumbar CSF in a clinical cohort from the Swedish BioFINDER study and postmortem ventricular CSF in a neuropathological cohort from the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program (AZSAND/BBDP). The BioFINDER cohort included 64 PD/PDD, 15 MSA, 15 PSP, 47 controls and two controls who later converted to PD/DLB. The neuropathological cohort included 101 cases with different brain disorders, including LBD and controls. In the BioFINDER cohort αSyn RT-QuIC identified LBD (i.e. PD, PDD and converters) vs. controls with a sensitivity of 95% and a specificity of 83%. The two controls that converted to LBD were αSyn RT-QuIC positive. Within the AZSAND/BBDP cohort, αSyn RT-QuIC identified neuropathologically verified "standard LBD" (i.e. PD, PD with AD and DLB; n = 25) vs. no LB pathology (n = 53) with high sensitivity (100%) and specificity (94%). Only 57% were αSyn RT-QuIC positive in the subgroup with "non-standard" LBD (i.e., AD with Lewy Bodies not meeting criteria for DLB or PD, and incidental LBD, n = 23). Furthermore, αSyn RT-QuIC reliably identified cases with LB pathology in the cortex (97% sensitivity) vs. cases with no LBs or LBs present only in the olfactory bulb (93% specificity). However, the sensitivity was low, only 50%, for cases with LB pathology restricted to the brainstem or amygdala, not affecting the allocortex or neocortex. In conclusion, αSyn RT-QuIC of CSF samples is highly sensitive and specific for identifying cases with clinicopathologically-defined Lewy body disorders and shows a lower sensitivity for non-standard LBD or asymptomatic LBD or in cases with modest LB pathology not affecting the cortex.
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,390
Funders: Michael J. Fox Foundation for Parkinson's Research, Eli Lilly and Company, Biogen, Arizona Department of Health Services, ACADIA Pharmaceuticals, Australian Government, Lunds Universitet, Eisai, Hjärnfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Alzheimerfonden, Skånes universitetssjukhus, Marcus och Amalia Wallenbergs minnesfond, Arizona Biomedical Research Commission, National Institutes of Health, University of California, San Diego, Parkinsonfonden, Avid Radiopharmaceuticals, National Institute on Aging, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1052080286, G1075639496, G1083877947, G1315589061, G1410864941, G1457535256, G1576660248, G1606131442, G2161113364, G250893170, G2898431357, Development of new biomarkers and brain imaging techniques for Dementia and Parkinsonian disorders: key tools for exploring etiology to improve diagnosis and advance drug development, G3228411741, G3250808129, G3251040009, G3480186095, G3521153818, G3540482749, G3687506083, G4028979961, G4193400840, G4791902628, G5166548482, G5184609404, G5193901556, G5585422332, G5619075, G6030318873, G6066643948, G6125194395, Arizona Alzheimer's Disease Core Center, G712881263, G7161884846, National Brain and Tissue Resource for Parkinson's Disease and Related Disorders, G7747731141, G7788227861, G7836467104, G7887587830, 3rd International Conference on Tomography of Materials and Structures, G7924111682, G837617365, G8508790466, G9000159448, G9000332211, UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, Arizona Alzheimer's Disease Research Center, G961669115
OpenAlex ID: W4283316648