Objective: Obstructive sleep apnea syndrome (OSAS) is characterized by nocturnal intermittent hypoxemia and can increase the risk of Parkinson's disease. This study aimed to investigate the association between plasma -synuclein levels and hypoxia in the patients with OSAS.
Methods: We recruited 42 OSAS patients and 46 controls with simple snoring matched for age and gender. OSAS was diagnosed on the basis of the clinical symptoms as well as the nighttime polysomnography. Plasma total -synuclein and phosphorylated -synuclein levels were measured by ELISA kits.
Results: The OSAS patients had significant higher levels of plasma total -synuclein and phosphorylated -synuclein levels. Both of the above indexes were positively correlated with the apnea-hypopnea index and the oxygen desaturation index, while they were negatively correlated with the mean and lowest oxyhemoglobin saturations.
Interpretation: This study suggests that chronic intermittent hypoxia can increase the -synuclein levels, which may contribute to the pathogenesis of Parkinson's disease.
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http://dx.doi.org/10.1002/acn3.756 | DOI Listing |
Alzheimers Dement
December 2024
New York University Grossman School of Medicine, New York, NY, USA.
Background: Synucleinopathies lack cures. Antibody therapies targeting α-synuclein aim to inhibit aggregation and enhance degradation, but have limited brain entry because of size (150kDa). Smaller single-domain antibodies (sdAbs, 15kDa) have substantially improved brain uptake.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Background: To identify discrete and continuous cell type signatures in brain tissue from donors with minimal cognitive decline despite harboring substantial proteinopathies associated with Alzheimer's Disease and Alzheimer's Disease-related dementias.
Method: Three large-scale single-nucleus RNA-seq studies on Alzheimer's Disease post-mortem human tissue were re-annotated and integrated to identify cell type composition associations with cognitive resilience to various neuropathologies. Cell type signatures were defined in two ways: using an integrated clustering approach and using a continuous factor-based analysis.
Background: Directed by the enzyme pair PINK1 and PRKN, mitophagy is a crucial mitochondrial quality control mechanism that selectively decorates damaged mitochondria with phosphorylated ubiquitin (pS65-Ub), facilitating their lysosomal degradation. The dynamic pS65-Ub signal accumulates upon enhanced activation from increased mitochondrial damage or upon reduced autophagic-lysosomal flux. Previous studies including ours demonstrated altered mitophagy and elevated pS65-Ub levels in Parkinson's and Alzheimer's disease brains that also independently associated with α-synuclein, tau, or amyloid pathology.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Background: Neurodegenerative disorders of aging are characterized by the progressive accumulation of proteins such as α-synuclein (α-syn) and amyloid beta (Aβ). Misfolded and aggregated α-syn has been implicated in neurological disorders such as Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB), but less so in Alzheimer's Disease (AD) despite the fact that synuclein pathology is present in over 50% of postmortem brains of AD patients. We are now expanding on our previous studies which showed positive therapeutic effects of downregulating α-syn in AD mice to understand the overall brain transcriptomic and mechanistic changes induced by treatment.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
Background: The role of oligomeric forms of various proteins as direct responsible of neuronal dysfunction in neurodegenerative disorders has been supported by numerous findings at experimental level and, more recently, by histological examinations in human material. The cellular prion protein (PrP) has been proposed to mediate the neurotoxicity of β-amyloid, α-synuclein and tau oligomers. We demonstrated that although amyloid-β oligomers (AβOs) bind with high affinity to PrP, the memory deficit induced by intracerebroventricular (ICV) administration of AβOs in mice was not mediated by PrP.
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