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https://www.readbyqxmd.com/read/29047416/lessons-learned-about-f-18-av-1451-off-target-binding-from-an-autopsy-confirmed-parkinson-s-case
#1
Marta Marquié, Eline E Verwer, Avery C Meltzer, Sally Ji Who Kim, Cinthya Agüero, Jose Gonzalez, Sara J Makaretz, Michael Siao Tick Chong, Prianca Ramanan, Ana C Amaral, Marc D Normandin, Charles R Vanderburg, Stephen N Gomperts, Keith A Johnson, Matthew P Frosch, Teresa Gómez-Isla
[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, including clinically normal whose brains are not expected to harbor tau pathology in those areas...
October 19, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29044415/morphologic-and-elemental-analysis-of-primary-melanosis-of-the-dentate-nucleus-review-and-correlation-with-neuromelanin
#2
Richard T Hopley, Edward Haller, Mumtaz V Rojiani, Amyn M Rojiani
Primary melanosis of the dentate nucleus is a rarely described entity with neither known cause nor definitive clinicopathologic correlation. We revisit this previously reported phenomenon by presenting one such case with a review of the pathology as well as additional investigations including elemental analysis by energy-dispersive X-ray, immunohistochemistry and electron microscopy. The lesion presented macroscopically as a sharply defined, black pigmentation that was restricted to the dentate nucleus of the cerebellum...
November 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28958075/mri-biomarkers-to-assess-substantia-nigra-damage-in-idiopathic-rem-sleep-behavior-disorder
#3
Nadya Pyatigorskaya, Rahul Gaurav, Dario Arnaldi, Smaranda Leu-Semenescu, Lydia Yahia-Cherif, Romain Valabregue, Marie Vidailhet, Isabelle Arnulf, Stephane Lehéricy
Objectives: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered to be a prodromal stage of Parkinson's disease (PD). At PD onset, 40 to 70% of the dopaminergic neurons in the substantia nigra (SN) are already lost. Thus, milder SN damage is expected in iRBD patients. We aimed to quantify SN damage in iRBD patients using multimodal MRI and to determine biomarker efficacy in preclinical Parkinsonism. Methods: Nineteen patients with iRBD and 18 controls underwent 3-Tesla MRI, including diffusion tensor imaging, neuromelanin (NM)-sensitive imaging and T2* mapping...
August 31, 2017: Sleep
https://www.readbyqxmd.com/read/28945963/the-analgesic-acetaminophen-and-the-antipsychotic-clozapine-can-each-redox-cycle-with-melanin
#4
Zülfikar Temoçin, Eunkyoung Kim, Jinyang Li, Lucia Panzella, Maria Laura Alfieri, Alessandra Napolitano, Deanna L Kelly, William E Bentley, Gregory F Payne
Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context...
October 9, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28943414/in-vivo-mri-assessment-of-the-human-locus-coeruleus-along-its-rostrocaudal-extent-in-young-and-older-adults
#5
Matthew J Betts, Arturo Cardenas-Blanco, Martin Kanowski, Frank Jessen, Emrah Düzel
The locus coeruleus (LC), a major origin of noradrenergic projections in the central nervous system (CNS), may serve a critical role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). As such, there is considerable interest to develop magnetic resonance imaging (MRI) techniques to assess the integrity of the LC in vivo. The high neuromelanin content of the LC serves as an endogenous contrast for MRI but existing protocols suffer from low spatial resolution along the rostrocaudal axis of the LC rendering it difficult to differentiate its integrity in caudal and rostral portions...
September 22, 2017: NeuroImage
https://www.readbyqxmd.com/read/28912300/-18-f-av-1451-binding-in-vivo-mirrors-the-expected-distribution-of-tdp-43-pathology-in-the-semantic-variant-of-primary-progressive-aphasia
#6
W R Bevan-Jones, Thomas E Cope, P Simon Jones, Luca Passamonti, Young T Hong, Tim D Fryer, Robert Arnold, Kieren S J Allinson, Jonathan P Coles, Franklin I Aigbirhio, Karalyn Patterson, John T O'Brien, James B Rowe
INTRODUCTION: Semantic dementia, including the semantic variant of primary progressive aphasia (svPPA), is strongly associated with TAR-DNA binding protein 43 (TDP-43) type C pathology. It provides a useful model in which to test the specificity of in vivo binding of the putative tau ligand [(18)F]AV-1451, which is elevated in frontotemporal lobar degeneration tauopathies. METHODS AND RESULTS: Seven patients (five with svPPA and two with 'right' semantic dementia) and 12 healthy controls underwent positron emission tomography brain imaging with [(18)F]AV-1451...
September 14, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28884232/-18-f-av-1451-binding-to-neuromelanin-in-the-substantia-nigra-in-pd-and-psp
#7
Sarah Coakeley, Sang Soo Cho, Yuko Koshimori, Pablo Rusjan, Christine Ghadery, Jinhee Kim, Anthony E Lang, Sylvain Houle, Antonio P Strafella
This study investigated binding of [(18)F]AV-1451 to neuromelanin in the substantia nigra of patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP). [(18)F]AV-1451 is a positron emission tomography radiotracer designed to bind pathological tau. A post-mortem study using [(18)F]AV-1451 discovered off-target binding properties to neuromelanin in the substantia nigra. A subsequent clinical study reported a 30% decrease in [(18)F]AV-1451 binding in the midbrain of PD patients. A total of 12 patients and 10 healthy age-matched controls were recruited...
September 7, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28879408/neuromelanin-in-parkinson-s-disease-from-fenton-reaction-to-calcium-signaling
#8
REVIEW
Rainer Knörle
Neuromelanin is supposed to play a key role in the pathogenesis of Parkinson's disease. A common theory is the formation of reactive oxygen species through the Fenton reaction catalyzed by neuromelanin-bound iron ions and subsequent death of the dopaminergic cells in the substantia nigra. From a physicochemical point of view, this pathway is rather implausible: a highly reactive radical built within a powerful radical scavenger would more promptly be inactivated before it might diffuse within the cell to reach a target to exert its deleterious potential...
September 6, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28763613/the-importance-of-mitophagy-in-maintaining-mitochondrial-function-in-u373mg-cells-bafilomycin-a1-restores-aminochrome-induced-mitochondrial-damage
#9
Sandro Huenchuguala, Patricia Muñoz, Juan Segura-Aguilar
Aminochrome, an orthoquinone formed during the dopamine oxidation of neuromelanin, is neurotoxic because it induces mitochondria dysfunction, protein degradation dysfunction (both autophagy and proteasomal systems), α-synuclein aggregation to neurotoxic oligomers, neuroinflammation, and oxidative and endoplasmic reticulum stress. In this study, we investigated the relationship between aminochrome-induced autophagy/lysosome dysfunction and mitochondrial dysfunction in U373MGsiGST6 cells. Aminochrome (75 μM) induces mitochondrial dysfunction as determined by (i) a significant decrease in ATP levels (70%; P < 0...
August 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28761417/on-the-role-of-endogenous-neurotoxins-and-neuroprotection-in-parkinson-s-disease
#10
REVIEW
Juan Segura-Aguilar
For 50 years ago was introduced L-3,4-dihydroxyphenylalanine (L-dopa) in Parkinson's disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson's disease...
June 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28743460/high-resolution-in-vivo-imaging-of-human-locus-coeruleus-by-magnetization-transfer-mri-at-3t-and-7t
#11
Nikos Priovoulos, Heidi I L Jacobs, Dimo Ivanov, Kamil Uludag, Frans R J Verhey, Benedikt A Poser
Locus Coeruleus (LC) is a neuromelanin-rich brainstem structure that is the source of noradrenaline in the cortex and is thought to modulate attention and memory. LC imaging in vivo is commonly performed with a 2D T1-weighted Turbo Spin Echo (TSE) MRI sequence, an approach that suffers from several drawbacks at 3T, including long acquisition times and highly anisotropic spatial resolution. In this study, we developed a high-resolution Magnetization Transfer (MT) sequence for LC imaging at both 7T and 3T and compared its performance to a TSE sequence...
July 22, 2017: NeuroImage
https://www.readbyqxmd.com/read/28743197/evaluation-of-parkinson-s-disease-by-neuromelanin-sensitive-magnetic-resonance-imaging-and-123-i-fp-cit-spect
#12
Keita Kuya, Toshihide Ogawa, Yuki Shinohara, Mana Ishibashi, Shinya Fujii, Naoko Mukuda, Yoshio Tanabe
Background Both neuromelanin-sensitive magnetic resonance imaging (NmMRI) and (123)I-FP-CIT single photon emission computed tomography (SPECT) (DaTSCAN) assist the diagnosis of Parkinson's disease (PD). However, there have been few studies investigating a correlation between them. Purpose To correlate the utility of NmMRI and DaTSCAN and to evaluate the relationship between both imaging findings and the Unified PD rating scale part III (UPDRS III) score for the diagnosis and management of PD. Material and Methods Seventeen patients with PD who underwent both NmMRI and DaTSCAN were included...
January 1, 2017: Acta Radiologica
https://www.readbyqxmd.com/read/28738061/magnetic-resonance-imaging-and-tensor-based-morphometry-in-the-mptp-non-human-primate-model-of-parkinson-s-disease
#13
Michel Modo, William R Crum, Madeline Gerwig, Anthony C Vernon, Priya Patel, Michael J Jackson, Sarah Rose, Peter Jenner, Mahmoud M Iravani
Parkinson's disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD...
2017: PloS One
https://www.readbyqxmd.com/read/28671143/substantia-nigra-neuromelanin-as-an-imaging-biomarker-of-disease-progression-in-parkinson-s-disease
#14
Margherita Fabbri, Sofia Reimão, Miguel Carvalho, Rita G Nunes, Daisy Abreu, Leonor Correia Guedes, Raquel Bouça, Patricia P Lobo, Catarina Godinho, Miguel Coelho, Nilza C Gonçalves, Mario Miguel Rosa, Angelo Antonini, Joaquim J Ferreira
BACKGROUND: A specific T1-weighted magnetic resonance imaging (MRI) sequence has been shown to detect substantia nigra (SN) neuromelanin (NM) signal changes that accurately discriminate Parkinson's disease (PD) patients from controls, even in early disease stages. However, it is unclear what happens to these SN changes in later disease stages and if they can be a marker of disease progression. OBJECTIVE: to investigate the pattern of SN-NM area loss and contrast ratio (CR) intensity changes in late-stage PD (LSPD) compared to earlier disease stages...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28655632/normative-data-of-dopaminergic-neurotransmission-functions-in-substantia-nigra-measured-with-mri-and-pet-neuromelanin-dopamine-synthesis-dopamine-transporters-and-dopamine-d2-receptors
#15
Hiroshi Ito, Hiroshi Kawaguchi, Fumitoshi Kodaka, Hiroyuki Takuwa, Yoko Ikoma, Hitoshi Shimada, Yasuyuki Kimura, Chie Seki, Hitoshi Kubo, Shiro Ishii, Harumasa Takano, Tetsuya Suhara
The central dopaminergic system is of major importance in the pathophysiology of Parkinson's disease, schizophrenia, and other neuropsychiatric disorders. In the present study, the normative data of dopaminergic neurotransmission functions in the midbrain, consisting of neuromelanin, dopamine synthesis, dopamine transporters and dopamine D2 receptors, were constructed using magnetic resonance (MR) imaging and positron emission tomography (PET). PET studies with L-[β-(11)C]DOPA, [(18)F]FE-PE2I and [(11)C]FLB457 and MRI studies were performed on healthy young men...
June 26, 2017: NeuroImage
https://www.readbyqxmd.com/read/28621758/brain-magnetic-resonance-imaging-mri-as-a-potential-biomarker-for-parkinson-s-disease-pd
#16
REVIEW
Paul Tuite
Magnetic resonance imaging (MRI) has the potential to serve as a biomarker for Parkinson's disease (PD). However, the type or types of biomarker it could provide remain to be determined. At this time there is not sufficient sensitivity or specificity for MRI to serve as an early diagnostic biomarker, i.e., it is unproven in its ability to determine if a single individual is normal, has mild PD, or has some other forms of degenerative parkinsonism. However there is accumulating evidence that MRI may be useful in staging and monitoring disease progression (staging biomarker), and also possibly as a means to monitor pathophysiological aspects of disease and associated response to treatments, i...
June 16, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28617379/-immunohistochemical-characteristics-of-the-substantia-nigra-neurons-of-the-human
#17
D E Korzhevskii, I P Grigor'ev, E G Sukhorukova, V V Gusel'nikova
AIM: To determine the cytochemical characteristics of unchanged neurons of the human substantia nigra using a wide range of immunocytochemical markers some of which (glutamate decarboxylase-65, PGP 9.5, non-phosphorylated neurofilament proteins, alpa-tubulin) have never been used for study of human dopaminergic neurons. MATERIAL AND METHODS: Fragments of human midbrain (17 men and women, aged from 28 to 78 years) from the archives of the Department of General and Specific Morphology of the Institute of Experimental Medicine were used...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28552865/new-development-of-diagnosis-and-treatment-for-parkinson-s-disease
#18
REVIEW
Satoshi Orimo
New methods for the diagnosis and new treatments for Parkinson's disease (PD) were explained. As imaging tools, neuromelanin imaging using brain MRI, meta-iodobenzylguanidine (MIBG) cardiac scintigraphy, dopamine transporter scintigraphy, and transcranial sonography were introduced. Olfactory dysfunction and REM sleep behavior disorders (RBD), which are important non-motor symptoms, and the new Clinical Criteria for PD launched by Movement Disorder Society (MDS) were also described. Investigative new medications and new anti-PD medications, which recently became available in Japan, were introduced...
June 28, 2017: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/28537985/neuroimaging-in-parkinson-s-disease-focus-on-substantia-nigra-and-nigro-striatal-projection
#19
Daniela Frosini, Mirco Cosottini, Duccio Volterrani, Roberto Ceravolo
PURPOSE OF REVIEW: The diagnosis of Parkinson disease is based on clinical features; however, unmet need is an imaging signature for Parkinson disease and the early differential diagnosis with atypical parkinsonisms. A summary of the molecular imaging and MRI recent evidences for Parkinson disease diagnosis will be presented in this review. RECENT FINDINGS: The nigro-striatal dysfunction explored by dopamine transporter imaging is not a mandatory diagnostic criterion for Parkinson disease, recent evidence supported its utility as in-vivo proof of degenerative parkinsonisms, and there might be compensatory mechanisms leading to an early overestimation...
August 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28533189/potential-therapeutic-effects-of-odorants-through-their-ectopic-receptors-in-pigmented-cells
#20
REVIEW
Barbara Pavan, Antonio Capuzzo, Alessandro Dalpiaz
Several olfactory receptors (ORs) have been characterized outside the olfactory neuroepithelium in neuronal and non-neuronal tissues, where they were implicated in the recognition of diverse chemical signals. ORs have been found to regulate melanogenesis in skin melanocytes, and OR expression has been found in the human brain nigrostriatal dopaminergic neurons, where production of melanin occurs as neuromelanin and can change with age; OR expression is downregulated in Parkinson's disease. Therefore, we propose several odorants as new functional ligands to ORs expressed in non-olfactory pigmented cells as dopaminergic neurons and melanocytes, where, by acting on cAMP-induced melanin production, they could help to counteract melanogenic and neurodegenerative dysfunctions, including melanoma and Parkinson's disease...
May 19, 2017: Drug Discovery Today
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