Striatal dopamine transporter binding differs between dementia with Lewy bodies and Parkinson’s disease with dementia

Ishizawa, Kunihiko; Fujita, Yukio; Nagashima, Kazuaki; Nakamura, Takumi; Shibata, Makoto; Kasahara, Hiroo; Makioka, Kouki; Taketomi-Takahashi, Ayako; Hirasawa, Hiromi; Higuchi, Tetsuya; Tsushima, Yoshito; Ikeda, Yoshio

doi:10.1016/j.jns.2023.120713

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…In another more recent study, Ishizawa et al ( 70 ) voxel-based analysis was used to examine striatal DAT binding patterns. Findings revealed that DAT binding was reduced in the posterior striatum in PD and PDD patients, in contrast to similar DAT binding levels observed in MSA-P, PSP, and DLB.…”

Section: Semi-quantitative Assessmentmentioning

confidence: 99%

Practical use of DAT SPECT imaging in diagnosing dementia with Lewy bodies: a US perspective of current guidelines and future directions

O’Shea,

Arkhipenko,

Galasko

et al. 2024

Front. Neurol.

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BackgroundDiagnosing Dementia with Lewy Bodies (DLB) remains a challenge in clinical practice. The use of 123I-ioflupane (DaTscan™) SPECT imaging, which detects reduced dopamine transporter (DAT) uptake—a key biomarker in DLB diagnosis—could improve diagnostic accuracy. However, DAT imaging is underutilized despite its potential, contributing to delays and suboptimal patient management.MethodsThis review evaluates DLB diagnostic practices and challenges faced within the U.S. by synthesizing information from current literature, consensus guidelines, expert opinions, and recent updates on DaTscan FDA filings. It contrasts DAT SPECT with alternative biomarkers, provides recommendations for when DAT SPECT imaging may be indicated and discusses the potential of emerging biomarkers in enhancing diagnostic approaches.ResultsThe radiopharmaceutical 123I-ioflupane for SPECT imaging was initially approved in Europe (2000) and later in the US (2011) for Parkinsonism/Essential Tremor. Its application was extended in 2022 to include the diagnosis of DLB. DaTscan’s diagnostic efficacy for DLB, with its sensitivity, specificity, and predictive values, confirms its clinical utility. However, US implementation faces challenges such as insurance barriers, costs, access issues, and regional availability disparities.Conclusion123I-ioflupane SPECT Imaging is indicated for DLB diagnosis and differential diagnosis of Alzheimer’s Disease, particularly in uncertain cases. Addressing diagnostic obstacles and enhancing physician-patient education could improve and expedite DLB diagnosis. Collaborative efforts among neurologists, geriatric psychiatrists, psychologists, and memory clinic staff are key to increasing diagnostic accuracy and care in DLB management.

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Section: Semi-quantitative Assessmentmentioning

confidence: 99%

Practical use of DAT SPECT imaging in diagnosing dementia with Lewy bodies: a US perspective of current guidelines and future directions

O’Shea,

Arkhipenko,

Galasko

et al. 2024

Front. Neurol.

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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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Striatal dopamine transporter binding differs between dementia with Lewy bodies and Parkinson’s disease with dementia

Cited by 2 publications

References 42 publications

Practical use of DAT SPECT imaging in diagnosing dementia with Lewy bodies: a US perspective of current guidelines and future directions

Practical use of DAT SPECT imaging in diagnosing dementia with Lewy bodies: a US perspective of current guidelines and future directions

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

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