Unexpected (123I)FP-CIT SPECT findings: SWIDD, SWEDD and all DAT

Balestrino, Roberta; Barone, Paolo; Filippi, Massimo; Erro, Roberto

doi:10.1007/s00415-021-10809-x

Cited by 5 publications

(1 citation statement)

References 100 publications

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“…This is a limitation of the examination, but it did not translate into statistical difference between databases. If the diagnosis of dopaminergic degeneration was to be confirmed at follow-up, these patients would be qualified as “Scan Without Evidence of Dopaminergic Deficit” (SWEDD), but according to a recent review [ 24 ], their proportion was estimated only to be about 2%, which is similar to the 2.5% alpha risk (− 2SD).…”

Section: Discussionmentioning

confidence: 99%

Semi-quantitative analysis of visually normal 123I-FP-CIT across three large databases revealed no difference between control and patients

et al. 2023

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Background To show the equivalence between the specific binding ratios (SBR) of visually normal 123I-FP-CIT SPECT scans from patients to those from healthy volunteers (Hv) or patients without dopaminergic degeneration to allow their use as a reference database. Methods The SBR values of visually normal SPECT scans from 3 groups were studied: (1) suspected Parkinsonism and no diagnostic follow-up (ScanOnlyDB: n = 764, NM/CT 670 CZT, GE Healthcare), (2) no degenerative dopaminergic pathology after a 5-year follow-up (NoDG5YearsDB: n = 237, Symbia T2, Siemens Medical Solutions), and 3) Hv (HvDB: n = 118, commercial GE database). A general linear model (GLM) was constructed with caudate, putamen, and striatum SBR as the dependent variables, and age and gender as the independent variables. Following post-reconstruction harmonization of the data, DB were combined in pairs, ScanOnlyDB&NoDG5yearsDG and ScanOnlyDB&HvDB before performing GLM analysis. Additionally, ScanOnlyDB GLM estimates were compared to those published from Siemens commercial DB (SiemensDB) and ENC-DAT. Results The dispersion parameters, R2 and the SBR coefficients of variation, did not differ between databases. For all volumes of interest and all databases, SBR decreased significantly with age (e.g., decrease per decade for the striatum: − 4.94% for ScanOnlyDB, − 4.65% for NoDG5YearsDB, − 5.69% for HvDB). There was a significant covariance between SBR and gender for ScanOnlyDB (P < 10–5) and NoDG5YearsDB (P < 10–2). The age-gender interaction was significant only for ScanOnlyDB (P < 10–2), and the p-value decreased to 10–6 after combining ScanOnlyDB with NoDG5YearsDB. ScanOnlyDB GLM estimates were not significantly different from those from SiemensDB or ENC-DAT except for age-gender interaction. Conclusion SBR values distribution from visually normal scans were not different from the existing reference database, enabling this method to create a reference database by expert nuclear physicians. In addition, it showed a rarely described age-gender interaction related to its size. The proposed post-reconstruction harmonization method can also facilitate the use of semi-quantitative analysis.

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Section: Discussionmentioning

confidence: 99%

Semi-quantitative analysis of visually normal 123I-FP-CIT across three large databases revealed no difference between control and patients

et al. 2023

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A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research

Simuni,

Chahine,

Poston

et al. 2024

The Lancet Neurology

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GDNF improves the cognitive ability of PD mice by promoting glycosylation and membrane distribution of DAT

Chengcheng,

Panpan,

Yalong

et al. 2024

Sci Rep

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The core of clinic treatment of Parkinson's disease (PD) is to enhance dopamine (DA) signaling within the brain. The regulation of dopamine transporter (DAT) is integral to this process. This study aims to explore the regulatory mechanism of glial cell line-derived neurotrophic factor (GDNF) on DAT, thereby gaining a profound understanding its potential value in treating PD. In this study, we investigated the effects of GDNF on both cellular and mouse models of PD, including the glycosylation and membrane transport of DAT detected by immunofluorescence and immunoblotting, DA signal measured by neurotransmitter fiber imaging technology, Golgi morphology observed by electron microscopic, as well as cognitive ability assessed by behavior tests. This study revealed that in animal trials, MPTP-induced Parkinson's Disease (PD) mice exhibited a marked decline in cognitive function. Utilizing ELISA and neurotransmitter fiber imaging techniques, we observed a decrease in dopamine levels and a significant reduction in the intensity of dopamine signal release in the Prefrontal Cortex (PFC) of PD mice induced by MPTP. Intriguingly, these alterations were reversed by Glial Cell Line-Derived Neurotrophic Factor (GDNF). In cellular experiments, following MPP + intervention, there was a decrease in Gly-DAT modification in both the cell membrane and cytoplasm, coupled with an increase in Nongly-DAT expression and aggregation of DAT within the cytoplasm. Conversely, GDNF augmented DAT glycosylation and facilitated its membrane transport in damaged dopaminergic neurons, concurrently reversing the effects of GRASP65 depletion and Golgi fragmentation, thereby reducing the accumulation of DAT in the Golgi apparatus. Furthermore, overexpression of GRASP65 enhanced DAT transport in PD cells and mice, while suppression of GRASP65 attenuated the efficacy of GDNF on DAT. Additionally, GDNF potentiated the reutilization of neurotransmitters by the PFC presynaptic membrane, boosting the effective release of dopamine following a single electrical stimulation, ultimately ameliorating the cognitive impairments in PD mice.Therefore, we propose that GDNF enhances the glycosylation and membrane trafficking of DAT by facilitating the re-aggregation of the Golgi apparatus, thereby amplifying the utilization of DA signals. This ultimately leads to the improvement of cognitive abilities in PD mouse models. Our study illuminates, from a novel angle, the beneficial role of GDNF in augmenting DA utilization and cognitive function in PD, providing fresh insights into its therapeutic potential.

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Unexpected (123I)FP-CIT SPECT findings: SWIDD, SWEDD and all DAT

Cited by 5 publications

References 100 publications

Semi-quantitative analysis of visually normal 123I-FP-CIT across three large databases revealed no difference between control and patients

Semi-quantitative analysis of visually normal 123I-FP-CIT across three large databases revealed no difference between control and patients

A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research

GDNF improves the cognitive ability of PD mice by promoting glycosylation and membrane distribution of DAT

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