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Lewy body diseases and the gut.
Mol Neurodegener
January 2025
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation.
View Article and Find Full Text PDFAPOEε4 alters ApoE and Fabp7 in frontal cortex white matter in prodromal Alzheimer's disease.
J Neuroinflammation
January 2025
Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, 85013, USA.
The ApoE ε4 allele (APOEε4) is a major genetic risk factor for sporadic Alzheimer's disease (AD) and is linked to demyelination and cognitive decline. However, its effects on the lipid transporters apolipoprotein E (ApoE) and fatty acid-binding protein 7 (Fabp7), which are crucial for the maintenance of myelin in white matter (WM) during the progression of AD remain underexplored. To evaluate the effects of APOEε4 on ApoE, Fabp7 and myelin in the WM of the frontal cortex (FC), we examined individuals carrying one ε4 allele that came to autopsy with a premortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI) and mild to moderate AD compared with non-carrier counterparts.
View Article and Find Full Text PDFIncreasing brain half-life of antibodies by additional binding to myelin oligodendrocyte glycoprotein, a CNS specific protein.
Fluids Barriers CNS
January 2025
Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven - University of Leuven, O&N II Herestraat 49 box 820, 3000, Leuven, Belgium.
Background: Therapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance.
View Article and Find Full Text PDFIdentifying novel heterozygous PI4KA variants in fetal abnormalities.
BMC Med Genomics
January 2025
Ultrasound Diagnosis Department, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, China.
Background: The clinical manifestations of PI4KA-related disorders are characterized by considerable variability, predominantly featuring neurological impairments, gastrointestinal symptoms, and a combined immunodeficiency. The aim of this study was to delineate the novel spectrum of PI4KA variants detected prenatally and to assess their influence on fetal development.
Methods: A thorough fetal ultrasound screening was conducted, supplemented by both antenatal and post-abortion magnetic resonance imaging (MRI) studies.
Severe pregnancy-associated atypical hemolytic uremia syndrome in the context of the COVID-19 pandemic: a novel survival case report.
BMC Pregnancy Childbirth
January 2025
Department of Intensive Care Medicine, Army Medical Center of PLA, No. 10 Changjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China.
Background: Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by uncontrolled activation of the complement system during pregnancy or the postpartum period. In the intensive care unit, aHUS must be differentiated from sepsis-related multiple organ dysfunction, thrombotic thrombocytopenic purpura (TTP), hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome. Early recognition of aHUS is critical for effective treatment and improved prognosis.
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