TY - JOUR
T1 - Radiological markers of CSF α-synuclein aggregation in Parkinson’s disease patients
AU - Droby, Amgad
AU - Yoffe-Vasiliev, Avital
AU - Atias, Daniel
AU - Fraser, Kyle B.
AU - Mabrouk, Omar S.
AU - Omer, Nurit
AU - Bar-Shira, Anat
AU - Gana-Weisz, Mali
AU - Goldstein, Orly
AU - Artzi, Moran
AU - Ben Bashat, Dafna
AU - Alcalay, Roy N.
AU - Orr-Urtreger, Avi
AU - Shirvan, Julia C.
AU - Cedarbaum, Jesse M.
AU - Giladi, Nir
AU - Mirelman, Anat
AU - Thaler, Avner
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Alpha-synuclein (αS) aggregation is a widely regarded hallmark of Parkinson’s disease (PD) and can be detected through synuclein amplification assays (SAA). This study investigated the association between cerebrospinal fluid (CSF) radiological measures in 41 PD patients (14 iPD, 14 GBA1-PD, 13 LRRK2-PD) and 14 age-and-sex-matched healthy controls. Quantitative measures including striatal binding ratios (SBR), whole-brain and deep gray matter volumes, neuromelanin-MRI (NM-MRI), functional connectivity (FC), and white matter (WM) diffusion-tensor imaging (DTI) were calculated. Nine LRRK2-PD patients were SAA-negative (PD-SAA−). PD-SAA+ patients showed lower whole-brain gray matter, putamenal, brainstem, and substantia nigra volumes, reduced FC in the left caudate, and lower fractional anisotropy in the left fronto-occipital fasciculus compared to PD-SAA−. Taken together, αS aggregation was observed in iPD, GBA1-PD, and 38% of LRRK2-PD patients, and this was associated with reduced regional brain volumes, altered caudal FC, and SBRs. These changes were less pronounced in PD-SAA−, possibly suggesting a milder neurodegenerative process.
AB - Alpha-synuclein (αS) aggregation is a widely regarded hallmark of Parkinson’s disease (PD) and can be detected through synuclein amplification assays (SAA). This study investigated the association between cerebrospinal fluid (CSF) radiological measures in 41 PD patients (14 iPD, 14 GBA1-PD, 13 LRRK2-PD) and 14 age-and-sex-matched healthy controls. Quantitative measures including striatal binding ratios (SBR), whole-brain and deep gray matter volumes, neuromelanin-MRI (NM-MRI), functional connectivity (FC), and white matter (WM) diffusion-tensor imaging (DTI) were calculated. Nine LRRK2-PD patients were SAA-negative (PD-SAA−). PD-SAA+ patients showed lower whole-brain gray matter, putamenal, brainstem, and substantia nigra volumes, reduced FC in the left caudate, and lower fractional anisotropy in the left fronto-occipital fasciculus compared to PD-SAA−. Taken together, αS aggregation was observed in iPD, GBA1-PD, and 38% of LRRK2-PD patients, and this was associated with reduced regional brain volumes, altered caudal FC, and SBRs. These changes were less pronounced in PD-SAA−, possibly suggesting a milder neurodegenerative process.
UR - http://www.scopus.com/inward/record.url?scp=85213982085&partnerID=8YFLogxK
U2 - 10.1038/s41531-024-00854-4
DO - 10.1038/s41531-024-00854-4
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C2 - 39753572
AN - SCOPUS:85213982085
SN - 2373-8057
VL - 11
JO - npj Parkinson's Disease
JF - npj Parkinson's Disease
IS - 1
M1 - 7
ER -
