Journal ArticleDOI
In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease.
Chong S. Lee,Ali Samii,Vesna Sossi,Thomas J. Ruth,Michael Schulzer,James E. Holden,Jess Wudel,Pramod Kumar Pal,Raúl de la Fuente-Fernández,Donald B. Calne,A. Jon Stoessl +10 more
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TLDR
Observations suggest that the activity of aromatic L‐amino acid decarboxylase is up‐regulated, whereas the plasma membrane DA transporter is down‐regulated in the striatum of patients with PD.Abstract:
Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine (DA) neuronal loss reaches a symptomatic threshold. To explore the mechanisms of functional compensation that occur in presynaptic DA nerve terminals in PD, we compared striatal positron emission tomographic (PET) measurements by using [11C]dihydrotetrabenazine ([11C]DTBZ; labeling the vesicular monoamine transporter type 2), [11C]methylphenidate (labeling the plasma membrane DA transporter), and [18F]dopa (reflecting synthesis and storage of DA). Three consecutive PET scans were performed in three-dimensional mode by using each tracer on 35 patients and 16 age-matched, normal controls. PET measurements by the three tracers were compared between subgroups of earlier and later stages of PD, between drug-naive and drug-treated subgroups of PD, and between subregions of the parkinsonian striatum. The quantitative relationships of [18F]dopa and [11]DTBZ, and of [11C]methylphenidate and [11C]DTBZ, were compared between the PD and the normal control subjects. We found that [18F]dopa Ki was reduced less than the binding potential (Bmax/Kd) for [11C]DTBZ in the parkinsonian striatum, whereas the [11C]methylphenidate binding potential was reduced more than [11C]DTBZ binding potential. These observations suggest that the activity of aromatic L-amino acid decarboxylase is up-regulated, whereas the plasma membrane DA transporter is down-regulated in the striatum of patients with PD.read more
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Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein.
Julie Lotharius,Patrik Brundin +1 more
TL;DR: It is proposed that defective sequestration of dopamine into vesicles, leading to the generation of reactive oxygen species in the cytoplasm, is a key event in the demise of dopaminergic neurons in Parkinson's disease and might represent a common pathway that underlies both genetic and sporadic forms of the disorder.
Journal ArticleDOI
Clinical progression in Parkinson disease and the neurobiology of axons.
TL;DR: It is proposed that ongoing degeneration of axons, not cell bodies, is the primary determinant of clinically apparent progression of disease, and that future experimental therapeutics intended to forestall disease progression will benefit from a new focus on the distinct mechanisms of axon degeneration.
Journal ArticleDOI
The cerebellum in Parkinson’s disease
Tao Wu,Mark Hallett +1 more
TL;DR: The role of the cerebellum in Parkinson's disease is investigated in this paper, where functional or morphological modulations were detected related to akinesia/rigidity, tremor, gait disturbance, dyskinesia and some non-motor symptoms.
Journal ArticleDOI
EFNS/MDS‐ES recommendations for the diagnosis of Parkinson's disease
Alfredo Berardelli,Gregor K. Wenning,Angelo Antonini,Daniela Berg,B.R. Bloem,Vincenzo Bonifati,David J. Brooks,David J. Burn,Carlo Colosimo,Alessandra Fanciulli,Joaquim J. Ferreira,Thomas Gasser,Francisco Grandas,Petr Kanovsky,Vladimir S. Kostic,Jaime Kulisevsky,Wolfgang H. Oertel,Werner Poewe,Jens P. Reese,Maja Relja,Evzem Ruzicka,A Schrag,Klaus Seppi,Pille Taba,Marie Vidailhet +24 more
TL;DR: A Task Force was convened by the EFNS/MDS‐ES Scientist Panel on Parkinson's disease and other movement disorders to systemically review relevant publications on the diagnosis of PD.
Journal ArticleDOI
Axon degeneration in Parkinson's disease.
TL;DR: It is proposed that a new focus on the neurobiology of axons, their molecular pathways of degeneration and growth, will offer novel opportunities for neuroprotection and restoration in the treatment of PD and other neurodegenerative diseases.
References
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Journal ArticleDOI
Ageing and parkinson's disease: substantia nigra regional selectivity
Julian Fearnley,Andrew J. Lees +1 more
TL;DR: It is suggested that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of Parkinson's disease and the regional selectivity of PD is relatively specific.
Journal ArticleDOI
Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations.
TL;DR: A clinical, morphological and neurochemical correlative study in patients with Parkinson's syndrome and Huntington's chorea is reported in this paper, where positive correlations can be established, within a certain range, between the severity of individual Parkinsonian symptoms (especially akinesia and tremor) and the degree, and also the site, of the disturbance of dopamine metabolism within the nuclei of the basal ganglia; and the sensitivity of the patients to levodopa's acute anti-akinesia effect.
Journal ArticleDOI
Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications.
TL;DR: It is proposed that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits are less marked or restricted to discrete functions only.
Journal ArticleDOI
Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations:
TL;DR: General equations are derived that can be used to analyze tissue uptake data when the blood–plasma concentration of the test substance cannot be easily measured and for situations when trapping of theTest substance is incomplete and for a combination of these two conditions.
Journal ArticleDOI
The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease.
TL;DR: The spatiotemporal progression of neuronal loss related to disease duration can be drawn in the substantia nigra pars compacta for each Parkinson's disease patient: depletion begins in the main pocket (nigrosome 1) and then spreads to other nigrosomes and the matrix along rostral, medial and dorsal axes of progression.
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