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Co-existing neuropathological comorbidities have been repeatedly reported to be extremely common in subjects dying with dementia due to Alzheimer disease. As these are likely to be additive to cognitive impairment, and may not be affected by molecularly-specific AD therapeutics, they may cause significant inter-individual response heterogeneity amongst subjects in AD clinical trials. Furthermore, while originally noted for the oldest old, recent reports have now documented high neuropathological comorbidity prevalences in younger old AD subjects, who are more likely to be included in clinical trials.
View Article and Find Full Text PDFThe anti-dyskinetic effect of the clinic-ready mGluRpositive allosteric modulator AZD8529 in the 6-OHDA-lesioned rat.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Neurodegenerative Disorders Research Group, Montreal Neurological Institute-Hospital (The Neuro), 3801 University St, Montreal, QC, H3A 2B4, Canada.
L-3,4-dihydroxyphenylalanine (L-DOPA) remains the main treatment for motor symptoms of Parkinson's disease (PD). However, chronic use is associated with the development of complications such as L-DOPA-induced dyskinesia. We previously demonstrated that LY-487,379, a highly selective metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator (PAM), reduces the severity of L-DOPA-induced abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD, without interfering with the anti-parkinsonian action of L-DOPA.
View Article and Find Full Text PDFCortical beta oscillation in brain slices of hemi parkinsonian mice.
Neurosci Lett
January 2025
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico. Electronic address:
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to significant motor and non-motor symptoms. Beta oscillations in cortical areas are a pathognomonic sign. Here we ask whether these oscillations can be recorded in in vitro cortical tissue despite severing the cortico-basal ganglia-thalamo-cortical loop.
View Article and Find Full Text PDFSynaptic Density Reductions in MSA: A Potential Biomarker Identified Through [F]SynVesT-1 PET Imaging.
Ann Neurol
January 2025
Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Objective: The objective of this study was to delineate synaptic density alterations in multiple system atrophy (MSA) and explore its potential role as a biomarker for MSA diagnosis and disease severity monitoring using [F]SynVesT-1 positron emission tomography / computed tomography (PET CT).
Methods: In this prospective study, 60 patients with MSA (30 patients with MSA-parkinsonian [MSA-P] subtype and 30 patients with MSA-cerebellar [MSA-C] subtype), 30 patients with Parkinson's disease (PD), and 30 age-matched healthy controls (HCs) underwent [F]SynVesT-1 PET/CT for synaptic density assessment. Visual, voxel, and volumetric region of interest (VOI) analyses were used to elucidate synaptic density patterns in the MSA brain and establish diagnostic criteria.
Leflunomide exerts neuroprotective effects in an MPTP‑treated mouse model of Parkinsonism.
Acta Neurobiol Exp (Wars)
January 2025
Ondokuz Mayıs University, School of Medicine, Department of Biochemistry, Samsun, Turkey.
Neuroinflammation and the immune response are recognized as significant mechanisms contributing to the progression and pathophysiology of Parkinson's disease (PD). Consequently, extensive research is being conducted on drugs targeting inflammation and immune response. Leflunomide, known for its anti‑inflammatory and immunomodulatory properties, is currently used as a disease‑modifying agent for the treatment of rheumatoid arthritis.
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