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Performance of αSyn...
Performance of αSynuclein RT-QuIC in relation to neuropathological staging of Lewy body disease
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- Hall, Sara (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Orrù, Christina D. (author)
- NIAID Rocky Mountain Laboratories
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- Serrano, Geidy E. (author)
- Banner Sun Health Research Institute
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- Galasko, Douglas (author)
- VA San Diego Healthcare System
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- Hughson, Andrew G. (author)
- NIAID Rocky Mountain Laboratories
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- Groveman, Bradley R. (author)
- NIAID Rocky Mountain Laboratories
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- Adler, Charles H. (author)
- Mayo Clinic Scottsdale-Phoenix, Arizona
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- Beach, Thomas G. (author)
- Banner Sun Health Research Institute
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- Caughey, Byron (author)
- NIAID Rocky Mountain Laboratories
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2022-06-22
- 2022
- English.
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In: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 10
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Autopsy
- Biomarkers
- Cerebrospinal fluid
- Dementia with Lewy bodies
- Diagnosis
- Lewy body dementia
- Parkinson disease
Publication and Content Type
- art (subject category)
- ref (subject category)
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Hall, Sara
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Orrù, Christina ...
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Serrano, Geidy E ...
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Galasko, Douglas
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Hughson, Andrew ...
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Groveman, Bradle ...
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Adler, Charles H ...
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Beach, Thomas G.
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Caughey, Byron
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Hansson, Oskar
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Acta Neuropathol ...
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Lund University