TY - JOUR
T1 - In vivo distribution of α-synuclein in multiple tissues and biofluids in Parkinson disease
AU - Chahine, Lana M.
AU - Beach, Thomas G.
AU - Brumm, Michael C.
AU - Adler, Charles H.
AU - Coffey, Christopher S.
AU - Mosovsky, Sherri
AU - Caspell-Garcia, Chelsea
AU - Serrano, Geidy E.
AU - Munoz, David G.
AU - White, Charles L.
AU - Crary, John F.
AU - Jennings, Danna
AU - Taylor, Peggy
AU - Foroud, Tatiana
AU - Arnedo, Vanessa
AU - Kopil, Catherine M.
AU - Riley, Lindsey
AU - Dave, Kuldip D.
AU - Mollenhauer, Brit
N1 - Funding Information:
The Article Processing Charge was funded by The Michael J. Fox Foundation for Parkinson's Research.
Publisher Copyright:
© American Academy of Neurology.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - ObjectiveThe Systemic Synuclein Sampling Study (S4) measured -synuclein in multiple tissues and biofluids within the same patients with Parkinson disease (PD) vs healthy controls (HCs).MethodsS4 was a 6-site cross-sectional observational study of participants with early, moderate, or advanced PD and HCs. Motor and nonmotor measures and dopamine transporter SPECT were obtained. Biopsies of skin, colon, submandibular gland (SMG), CSF, saliva, and blood were collected. Tissue biopsy sections were stained with 5C12 monoclonal antibody against pathologic α-synuclein; digital images were interpreted by neuropathologists blinded to diagnosis. Biofluid total α-synuclein was quantified using ELISA.ResultsThe final cohort included 59 patients with PD and 21 HCs. CSF α-synuclein was lower in patients with PD vs HCs; sensitivity/specificity of CSF α-synuclein for PD diagnosis was 87.0%/63.2%, respectively. Sensitivity of α-synuclein immunoreactivity for PD diagnosis was 56.1% for SMG and 24.1% for skin; specificity was 92.9% and 100%, respectively. There were no significant relationships between different measures of α-synuclein within participants.ConclusionsS4 confirms lower total α-synuclein levels in CSF in patients with PD compared to HCs, but specificity is low. In contrast, α-synuclein immunoreactivity in skin and SMG is specific for PD but sensitivity is low. Relationships within participants across different tissues and biofluids could not be demonstrated. Measures of pathologic forms of α-synuclein with higher accuracy are critically needed.Classification of evidenceThis study provides Class III evidence that total CSF α-synuclein does not accurately distinguish patients with PD from HCs, and that monoclonal antibody staining for SMG and skin total α-synuclein is specific but not sensitive for PD diagnosis.
AB - ObjectiveThe Systemic Synuclein Sampling Study (S4) measured -synuclein in multiple tissues and biofluids within the same patients with Parkinson disease (PD) vs healthy controls (HCs).MethodsS4 was a 6-site cross-sectional observational study of participants with early, moderate, or advanced PD and HCs. Motor and nonmotor measures and dopamine transporter SPECT were obtained. Biopsies of skin, colon, submandibular gland (SMG), CSF, saliva, and blood were collected. Tissue biopsy sections were stained with 5C12 monoclonal antibody against pathologic α-synuclein; digital images were interpreted by neuropathologists blinded to diagnosis. Biofluid total α-synuclein was quantified using ELISA.ResultsThe final cohort included 59 patients with PD and 21 HCs. CSF α-synuclein was lower in patients with PD vs HCs; sensitivity/specificity of CSF α-synuclein for PD diagnosis was 87.0%/63.2%, respectively. Sensitivity of α-synuclein immunoreactivity for PD diagnosis was 56.1% for SMG and 24.1% for skin; specificity was 92.9% and 100%, respectively. There were no significant relationships between different measures of α-synuclein within participants.ConclusionsS4 confirms lower total α-synuclein levels in CSF in patients with PD compared to HCs, but specificity is low. In contrast, α-synuclein immunoreactivity in skin and SMG is specific for PD but sensitivity is low. Relationships within participants across different tissues and biofluids could not be demonstrated. Measures of pathologic forms of α-synuclein with higher accuracy are critically needed.Classification of evidenceThis study provides Class III evidence that total CSF α-synuclein does not accurately distinguish patients with PD from HCs, and that monoclonal antibody staining for SMG and skin total α-synuclein is specific but not sensitive for PD diagnosis.
UR - http://www.scopus.com/inward/record.url?scp=85090175131&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000010404
DO - 10.1212/WNL.0000000000010404
M3 - Article
C2 - 32747521
AN - SCOPUS:85090175131
SN - 0028-3878
VL - 95
SP - E1267-E1284
JO - Neurology
JF - Neurology
IS - 9
ER -