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- Pharmacological combinations in early stages of Parkinson (C1 M3, Ground floor) - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1552;
There is heterogeneity in drug combinations used in early PD, but most patients are on Ldopa after three years. The longitudinal analysis shows that drug combinations without Ldopa are associated with a lower risk of developing dyskinesias.
- Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Supernus Pharma
Efficacy and safety of safinamide in PD patients over 70 years vs. under 70 years old; () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1535;
No statistically significant differences were found regarding the safety and efficacy of safinamide between groups. However, this sample has shown that postural instability and cognitive symptoms may possibly predict safinamide
- Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Supernus Pharma
The efficacy of dopamine agonists or monoamine oxidase type B inhibitors as monotherapy in patients with early Parkinson disease: A network meta-analysis () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1528;
However, this sample has shown that postural instability and cognitive symptoms may possibly predict safinamide This network meta-analysis suggests that pramipexole, rotigotine, rasagiline, and selegiline are effective monotherapy options for patients with early PD.
- rasagiline / Generic mfg.
Rasagiline in Chinese patients with early-stage parkinson () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1463;
This network meta-analysis suggests that pramipexole, rotigotine, rasagiline, and selegiline are effective monotherapy options for patients with early PD. Early treatment with rasagiline 1 mg/day was effective in improving symptoms for Chinese patients with early-stage PD, and the early-start treatment showed a potential disease-modifying effect.
- prasinezumab (RG7935) / Roche
A Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants With Early Parkinson () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1436;
P2b
The PADOVA study population is suitable for investigating the potential of prasinezumab to slow disease progression in individuals with early PD on stable symptomatic therapy. Trial Registration: NCT04777331.
- Does baseline expectation of benefit predict outcome in SURE-PD3, a Randomized, Double-Blind, Placebo-Controlled, Phase III trial of Inosine in Parkinson () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1432;
P3
Our results do not support an association between patient-reported baseline expected benefit from a potentially disease-modifying experimental therapy or treatment preference and clinical trial efficacy outcomes. In the context of disease-modification trials in PD, it is possible that the participant experiences during the clinical trial, including ongoing interactions with study staff, modifies pre-treatment attitudes and changes the magnitude of placebo and lessebo effects.
- Comtan (entacapone) / Novartis, Orion Corp
Long-term effectiveness of adjuvant treatment with catechol-o-methyltransferase or monoamine oxidase B inhibitors compared with dopamine agonists in Parkinson () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1379;
There was no difference in patient-rated QoL between DA and DDI therapy. However, QoL was somewhat better in patients receiving MAOB or DA than COMT inhibitors.
- 15-year effects of initiating treatment for Parkinson () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1378;
Patient-rated QoL was slightly better in patients receiving LD than LD-sparing therapy, in spite of the small increase in dyskinesia, with benefits maintained through 15 years of follow-up. MAOB inhibitors appeared as effective as DA as LD-sparing therapy.
- Duodopa (levodopa/carbidopa intraduodenal gel infusion) / AbbVie
Use of concomitant medications before and after treatment with levodopa/carbidopa intestinal gel in patients with advanced Parkinson () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1367;
P3
MAOB inhibitors appeared as effective as DA as LD-sparing therapy. Overall, in patients with advanced PD, treatment with LCIG was associated with decreased use of most major classes of oral PD medications, with a considerable proportion of patients using LCIG monotherapy, thereby potentially minimizing the complexity of therapeutic regimens and contributing to reduced pill burden.
- selegiline / Generic mfg.
The monoamine oxidase-B inhibitor selegiline does not affect 18F-Florzolotau uptake in patients with progressive supranuclear palsy: a longitudinal case series () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_701;
Overall, in patients with advanced PD, treatment with LCIG was associated with decreased use of most major classes of oral PD medications, with a considerable proportion of patients using LCIG monotherapy, thereby potentially minimizing the complexity of therapeutic regimens and contributing to reduced pill burden. The interpretation of F-Florzolotau PET images, with respect to tau pathology, is not confounded by MAO-B availability.
- || Clinical, Journal: A Randomized, Double-Blind, Placebo-Controlled Study of an Anthocyanin-Rich Functional Ingredient on Cognitive Function and Eye Dryness in Late Adulthood Volunteers: Roles of Epigenetic and Gut Microbiome Modulations. (Pubmed Central) - Aug 30, 2023
but decreased pH in feces. These data suggest that "Anthaplex" improves cognitive function and eye dryness via the modulations of the histone acetylation process, gut microbiome, and cholinergic function.
- | Journal: Assembling a Cinnamyl Pharmacophore in the C3-Position of Substituted Isatins via Microwave-Assisted Synthesis: Development of a New Class of Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson's Disease. (Pubmed Central) - Aug 30, 2023
A molecular docking study of the lead molecule was also performed to determine hypothetical interactions in the enzyme-binding cavity. These findings suggest that IHC3 is a strong, specific, and reversible MAO-B inhibitor that can be used to treat neurological diseases.
- || Review, Journal: Pharmacological and Non-Pharmacological Treatments for Depression in Parkinson's Disease: An Updated Review. (Pubmed Central) - Aug 30, 2023
Herein, we aim to provide an updated comprehensive review of both pharmacological and non-pharmacological treatments for depression in PD, focusing on recent clinical trials, systematic reviews, and meta-analyses. Finally, we discuss the pharmacological agents that are currently under investigation at a clinical level, as well as future approaches based on the pathophysiological mechanisms underlying the onset of depression in PD.
- | Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Supernus Pharma
Journal: An efficient method to access spiro pseudoindoxyl ketones: evaluation of indoxyl and their N-benzylated derivatives for inhibition of the activity of monoamine oxidases. (Pubmed Central) - Aug 24, 2023
In a reversibility experiment using dialysis, 11f showed effective recovery of MAO-B inhibition similar to that of safinamide. These experiments suggested that 11f was a potent, reversible, and competitive inhibitor of MAO-B activity.
- | Journal: Astrogliosis marker 11C-SL2511.88 PET in traumatic brain injury with persistent symptoms. (Pubmed Central) - Aug 21, 2023
Elevated [11C]SL25.1188 VT argues strongly for astrogliosis and therapeutics modifying astrogliosis towards curative phenotypes should be tested in TBI with persistent symptoms. Given substantive effect size, astrogliosis PET markers should be applied to stratify cases and/or assess target engagement for putative therapeutics targeting astrogliosis.
- | enzalutamide capsule / Generic mfg., phenelzine / Generic mfg.
Journal: Synthesis and anti-cancer potential of potent peripheral MAOA inhibitors designed to limit blood:brain penetration. (Pubmed Central) - Aug 21, 2023
A Phase II Clinical Trial has demonstrated the therapeutic effects of the irreversible nonselective MAOi phenelzine for prostate cancer...However, introduction of a polar 2-hydroxy in the propyl chain retained the highly selective MAOA inhibition and cancer cell cytotoxicity of clorgyline while reducing its CNS score from 2 to 0. We believe that these results identify a new class of peripherally directed MAOIs that may allow safer therapeutic targeting of MAOA for a variety of anti-cancer and anti-inflammatory indications.
- | donepezil / Generic mfg.
Journal: Investigation on Novel E/Z 2-Benzylideneindan-1-One-Based Photoswitches with AChE and MAO-B Dual Inhibitory Activity. (Pubmed Central) - Aug 16, 2023
Recently, combining a photopharmacology approach with the multitarget-directed ligand (MTDL) design strategy, we disclosed a novel donepezil-like compound, namely 2-(4-((diethylamino)methyl)benzylidene)-5-methoxy-2,3-dihydro-1H-inden-1-one (1a), which in the E isomeric form (and about tenfold less in the UV-B photo-induced isomer Z) showed the best activity as dual inhibitor of the AD-related targets acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B)...The pure E-isomer of the N-benzyl(ethyl)amino analog 1h achieved low nanomolar AChE and high nanomolar MAO-B inhibition potencies (ICs 39 and 355 nM, respectively), whereas photoisomerization to the Z isomer (75% Z in the PSS mixture) resulted in a decrease (about 30%) of AChE inhibitory potency, and not in the MAO-B one. Molecular docking studies were performed to rationalize the different E/Z selectivity of 1h toward the two target enzymes.
- | Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Supernus Pharma
Preclinical, Journal: Analgesic effect of safinamide mesylate in a rat model of neuropathic pain. (Pubmed Central) - Aug 14, 2023
The present findings show that safinamide improves neuropathic pain in male CCI model rats. Further animal model research and pathological and molecular pharmacological investigations are warranted.
- | Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Supernus Pharma
Journal: Evaluation of developmental toxicity of safinamide in zebrafish larvae (Danio rerio). (Pubmed Central) - Aug 9, 2023
Transcriptome analysis identified that safinamide exposure may disturb a variety of physiological processes such as neuroactive ligand-receptor interaction signaling pathway. In summary, our study reveals that safinamide may cause developmental defects in zebrafish larvae and provides insights into its toxic reactions in early develoment.
- | betahistine / Generic mfg.
Preclinical, Journal: Dose- and application route-dependent effects of betahistine on behavioral recovery and neuroplasticity after acute unilateral labyrinthectomy in rats. (Pubmed Central) - Aug 4, 2023
This may be achieved by higher doses, inhibition of MAO-based metabolism, or a parenteral route. In vivo imaging suggests a drug-target engagement in central vestibular networks.
- | Journal: Xanthine-Dopamine Hybrid Molecules as Multitarget Drugs with Potential for the Treatment of Neurodegenerative Diseases. (Pubmed Central) - Aug 2, 2023
As a result, protective effects against oxidative stress in neuroblastoma cells were observed, confirming the utility of the applied strategy. Further evaluation of the newly developed multitarget ligands in preclinical models of Alzheimer's and Parkinson's diseases is warranted.
- | Preclinical, Journal: Pharmacological bioactivity of Ceratonia siliqua pulp extract: in vitro screening and molecular docking analysis, implication of Keap-1/Nrf2/NF-?B pathway. (Pubmed Central) - Jul 31, 2023
When contrasting data from molecular docking, it was reported that both apigenin-7-glucoside and rutin in CS-PAE have a good affinity toward the Keap-1/Nrf2/ NF-?B pathway. In conclusion, CS-PAE showed promise in therapeutic activity in metabolic conditions.
- | Cognex (tacrine) / Shionogi
Journal: Modified Tacrine Derivatives as Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Synthesis, Biological Evaluation, and Molecular Modeling Study. (Pubmed Central) - Jul 31, 2023
It was shown that 5c and 5d were blood-brain barrier (BBB) penetrants by online prediction. Taken together, these multifunctional properties highlight that compounds 5c and 5d can serve as promising candidates for the further development of multifunctional drugs against AD.
- | Journal: Expression of Amine Oxidase Proteins in Adrenal Cortical Neoplasm and Pheochromocytoma. (Pubmed Central) - Jul 29, 2023
In the univariate analysis, low MAOA expression in stromal cells of ACN was associated with shorter overall survival (p = 0.008). In conclusion, monoamine oxidase proteins revealed differences in expression between ACN and PCC and also between benign and malignant cells.
- || Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Supernus Pharma
Preclinical, Review, Journal: Type-B monoamine oxidase inhibitors in neurological diseases: clinical applications based on preclinical findings. (Pubmed Central) - Jul 25, 2023
The potential fields of application concern epilepsy, Duchenne muscular dystrophy, multiple sclerosis, and above all, ischemic brain injury. The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline, rasagiline, and safinamide in Parkinson's disease and beyond, focusing on possible future therapeutic applications.
- || Review, Journal: Nature as a source and inspiration for human monoamine oxidase B (Hmao-B) inhibition: A review of the recent advances in chemical modification of natural compounds. (Pubmed Central) - Jul 19, 2023
All the natural scaffolds herein presented displayed a broad chemical diversity. The knowledge of their biological activity as inhibitors of hMAO-B enzyme allows the positive correlations associated with the consumption of specific food or the possible herb-drug interactions and suggests to the Medicinal Chemists how to address chemical functionalization to obtain more potent and selective compounds.
- | Journal: Exploration of a new class of monoamine oxidase B inhibitors by assembling benzyloxy pharmacophore on halogenated chalcones. (Pubmed Central) - Jul 17, 2023
Based on the modelling results, BB4 showed a stable confirmation during the dynamic simulation. From these results, it was concluded that BB2 and BB4 were potent selective reversible MAO-B inhibitors and they can be considered drug candidates for treating related neurodegenerative diseases such as Parkinson's disease.
- | Journal: Halogenated class of oximes as a new class of monoamine oxidase-B inhibitors for the treatment of Parkinson's disease: Synthesis, biochemistry, and molecular dynamics study. (Pubmed Central) - Jul 14, 2023
Molecular docking and dynamics showed the stable binding mode of the lead molecule CHBO4 on the active site of hMAO-B. These results suggest that CHBO4 is a potent reversible, competitive, and selective hMAO-B inhibitor and can be used as a treatment agent for neurological disorders.
- Deciphering the role of p-tau, iron and MAOB in neurobiological basis of F18-flortaucipir signal with voxel-to-voxel histology to PET analysis in different tauopathies (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_8540;
Iron deposits contributed to Flortaucipir uptake in regions both with or without histopathologically confirmed p-tau, including basal ganglia, whereas MAOB contribution was almost null in gray matter . The time gap between PET and autopsy and lower PET resolution compared to histology may explain the moderate regression coefficients, but other unexplored contributors cannot be discarded.
- Validation of A Novel MAO-B PET tracer [18F]SMBT-1 on postmortem human brain samples (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_7930;
accumulation. [ 18 F]SMBT-1 would be a promising marker for reactive astrogliosis in neurodegenerative diseases.
- Sex differences of cerebrospinal fluid biomarkers in Alzheimer's disease (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_7180;
[ 18 F]SMBT-1 would be a promising marker for reactive astrogliosis in neurodegenerative diseases. Both CSF levels of HVA and 5HIAA were significantly higher in women in AD, presumably due to increased MAO activity.
- hyoscine butylbromide oral / Generic mfg.
"Unraveling the Neuroprotective Mechanism of Dioscorea bulbifera (DB) in Alzheimer's Disease (AD) Caused by Estrogen Loss: An Integrated Network Pharmacology Investigation and Experimental Validation" (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_7040;
Our findings provide experimental support for the predicted mechanism of action of DB in AD caused by estrogen loss, and validate its neuroprotective effects using behavioral tests and ELISA in ovariectomized rats. DB may hold promise as a potential therapeutic option for AD, particularly in the context of estrogen loss, and further research is warranted to explore its full potential in AD treatment.
- selegiline / Generic mfg.
Update on [18F]ACI-12589: a novel and promising PET tracer for a-synuclein (Hall 2) - Jul 6, 2023 - Abstract #AAIC2023AAIC_6986;
[ 18 F]ACI-12589 displays the preclinical and clinical characteristics deemed necessary to become a reliable and accurate PET radiotracer for the detection of a-syn pathology in MSA. Additional evaluations of this tracer will focus on the longitudinal and early disease stage assessments.
- Validation of A Novel MAO-B PET tracer [18F]SMBT-1 on postmortem human brain samples (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_5864;
accumulation. [ 18 F]SMBT-1 would be a promising marker for reactive astrogliosis in neurodegenerative diseases.
- Sex differences of cerebrospinal fluid biomarkers in Alzheimer's disease (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_5114;
[ 18 F]SMBT-1 would be a promising marker for reactive astrogliosis in neurodegenerative diseases. Both CSF levels of HVA and 5HIAA were significantly higher in women in AD, presumably due to increased MAO activity.
- hyoscine butylbromide oral / Generic mfg.
"Unraveling the Neuroprotective Mechanism of Dioscorea bulbifera (DB) in Alzheimer's Disease (AD) Caused by Estrogen Loss: An Integrated Network Pharmacology Investigation and Experimental Validation" (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_4973;
Our findings provide experimental support for the predicted mechanism of action of DB in AD caused by estrogen loss, and validate its neuroprotective effects using behavioral tests and ELISA in ovariectomized rats. DB may hold promise as a potential therapeutic option for AD, particularly in the context of estrogen loss, and further research is warranted to explore its full potential in AD treatment.
- In vivo [18F]SMBT-1 imaging of reactive astrocytes in mouse models of Alzheimer (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_4703;
DB may hold promise as a potential therapeutic option for AD, particularly in the context of estrogen loss, and further research is warranted to explore its full potential in AD treatment. The findings provide in vivo evidence for different regional distribution of reactive astrocytes and microgliosis in animal models of AD.
- Assessing reactive astrogliosis in Parkinson (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_4020;
The first study to assess reactive astrogliosis signature in postmortem PD brains with astroglial tracers BU99008 and DED. The findings clearly highlight regional differences in BU99008 and DED binding in PD brains and suggest increased reactive astrogliosis at the end stages of the disease warrants further investigation.
- Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Supernus Pharma
Neuroprotective potential of safinamide mesylate in streptozotocin induced sporadic Alzheimer (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_3990;
The findings clearly highlight regional differences in BU99008 and DED binding in PD brains and suggest increased reactive astrogliosis at the end stages of the disease warrants further investigation. Based on the outcomes of the current investigations it would be safe to conclude that safinamide mesylate has neuroprotective potential and the observed cognitive enhancement in STZ rats following safinamide mesylate treatment may be due to its antioxidant potential and its ability to protect or preserve neuronal cells.
- Validation of A Novel MAO-B PET tracer [18F]SMBT-1 on postmortem human brain samples (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_3618;
accumulation. [ 18 F]SMBT-1 would be a promising marker for reactive astrogliosis in neurodegenerative diseases.
- Sex differences of cerebrospinal fluid biomarkers in Alzheimer's disease (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_2868;
[ 18 F]SMBT-1 would be a promising marker for reactive astrogliosis in neurodegenerative diseases. Both CSF levels of HVA and 5HIAA were significantly higher in women in AD, presumably due to increased MAO activity.
- hyoscine butylbromide oral / Generic mfg.
"Unraveling the Neuroprotective Mechanism of Dioscorea bulbifera (DB) in Alzheimer's Disease (AD) Caused by Estrogen Loss: An Integrated Network Pharmacology Investigation and Experimental Validation" (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_2728;
Our findings provide experimental support for the predicted mechanism of action of DB in AD caused by estrogen loss, and validate its neuroprotective effects using behavioral tests and ELISA in ovariectomized rats. DB may hold promise as a potential therapeutic option for AD, particularly in the context of estrogen loss, and further research is warranted to explore its full potential in AD treatment.
- donepezil / Generic mfg.
Donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_2473;
protein fragments that accumulate in the brain. The pharmacological profile of compound 11, as well as the fact that it is a readily available compound in a short synthetic sequence, in good chemical yields, prompts us to select it as a lead-compound for further optimization in our current research programme targeted to the preparation of new molecules for the potential treatment of AD.
- Electrophysiological effects of mitochondria-derived extracellular vesicles: implications for memory dysfunction in neurodegenerative disorders (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_1880;
The pharmacological profile of compound 11, as well as the fact that it is a readily available compound in a short synthetic sequence, in good chemical yields, prompts us to select it as a lead-compound for further optimization in our current research programme targeted to the preparation of new molecules for the potential treatment of AD. Pathogenic mitovesicles are previously undescribed active players of the brain extracellular milieu by regulating LTP via MAO-B, and potentially contribute to memory formation deficiencies typically found in AD and DS.
- Design, synthesis, and biological evaluation of Propargylated phenyl-styryl-pyrimidine derivatives as dual inhibitors of monoamine oxidase and acetylcholinesterase (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_1700;
VKB-14 was found as potential lead, which showed good inhibition against both AChE and MAO-B enzymes. It can be further optimized as MTDL for the treatment of AD.
- Validation of A Novel MAO-B PET tracer [18F]SMBT-1 on postmortem human brain samples (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_1398;
accumulation. [ 18 F]SMBT-1 would be a promising marker for reactive astrogliosis in neurodegenerative diseases.
- Sex differences of cerebrospinal fluid biomarkers in Alzheimer's disease (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_648;
[ 18 F]SMBT-1 would be a promising marker for reactive astrogliosis in neurodegenerative diseases. Both CSF levels of HVA and 5HIAA were significantly higher in women in AD, presumably due to increased MAO activity.
- hyoscine butylbromide oral / Generic mfg.
"Unraveling the Neuroprotective Mechanism of Dioscorea bulbifera (DB) in Alzheimer's Disease (AD) Caused by Estrogen Loss: An Integrated Network Pharmacology Investigation and Experimental Validation" (Virtual) - Jul 6, 2023 - Abstract #AAIC2023AAIC_509;
Our findings provide experimental support for the predicted mechanism of action of DB in AD caused by estrogen loss, and validate its neuroprotective effects using behavioral tests and ELISA in ovariectomized rats. DB may hold promise as a potential therapeutic option for AD, particularly in the context of estrogen loss, and further research is warranted to explore its full potential in AD treatment.
- Deciphering the role of p-tau, iron and MAOB in neurobiological basis of F18-flortaucipir signal with voxel-to-voxel histology to PET analysis in different tauopathies (Hall 2 (RAI Amsterdam Convention Centre)) - Jul 6, 2023 - Abstract #AAIC2023AAIC_459;
Iron deposits contributed to Flortaucipir uptake in regions both with or without histopathologically confirmed p-tau, including basal ganglia, whereas MAOB contribution was almost null in gray matter. The time gap between PET and autopsy and lower PET resolution compared to histology may explain the moderate regression coefficients, but other unexplored contributors cannot be discarded.
- Assessing reactive astrogliosis in Parkinson (Hall 1 (RAI Amsterdam Convention Centre); In Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_143;
The first study to assess reactive astrogliosis signature in postmortem PD brains with astroglial tracers BU99008 and DED. The findings clearly highlight regional differences in BU99008 and DED binding in PD brains and suggest increased reactive astrogliosis at the end stages of the disease warrants further investigation.