Amyloid in blood

BACKGROUND: In selected cases of cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is combined with trans valvular micro axial flow pumps (ECMELLA). Observational studies indicate that ECMELLA may reduce mortality but exposing the patient to two advanced mechanical support devices may affect the early inflammatory response. We aimed to explore inflammatory biomarkers in a porcine cardiogenic shock model managed with V-A ECMO or ECMELLA. METHODS: Fourteen landrace pigs had acute myocardial infarction-induced cardiogenic shock with minimal arterial pulsatility by microsphere embolization and were afterwards managed 1:1 with either V-A ECMO or ECMELLA for 4 h...

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions...

Central nervous system disorders are prevalent, profoundly debilitating, and poorly managed. Developing innovative treatments for these conditions, including Alzheimer's disease, could significantly improve patients' quality of life and reduce the future economic burden on healthcare systems. However, groundbreaking drugs for central nervous system disorders have been scarce in recent years, highlighting the pressing need for advancements in this field. One significant challenge in the realm of nanotherapeutics is ensuring the precise delivery of drugs to their intended targets due to the complex nature of Alzheimer's disease...

Monoclonal antibodies (mAbs) that target the P-amyloid peptide (Aβ) are important Alzheimer's disease research tools and are now being used as Alzheimer's disease therapies. Conformation-specific mAbs that target oligomeric and fibrillar Aβ assemblies are of particular interest, as these assemblies are associated with Alzheimer's disease pathogenesis and progression. This paper reports the generation of rabbit mAbs against two different triangular trimers derived from Aβ. These antibodies are the first mAbs generated against Aβ oligomer mimics in which the high-resolution structures of the oligomers are known...

We aimed to test the hypothesis that repeated muscle collections would impact mitochondrial function, antioxidant status, and markers of inflammation and muscle damage. Twenty-six horses (8 geldings, 18 mares; mean±SD 9.5±3.5 y) had gluteus medius muscle biopsy samples collected at: 0 and 24h (n=7); 0 and 6h (n=6); 0, 6, and 12h (n=7); or 0, 6, 12, and 24h (n=6). Blood was collected from all horses every 6h for 72h, starting 24h prior to the 0h muscle collection. Data were analyzed using mixed linear models...

Alzheimer's disease (AD) is a chronic neurodegenerative disorder with a global impact. The past few decades have witnessed significant strides in comprehending the underlying pathophysiological mechanisms and developing diagnostic methodologies for AD, such as neuroimaging approaches. Neuroimaging techniques, including positron emission tomography and magnetic resonance imaging, have revolutionized the field by providing valuable insights into the structural and functional alterations in the brains of individuals with AD...

Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of cerebral small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They are prevalent in the aging population, with multiple CMHs often being observed in a given individual. CMHs are closely associated with accelerated cognitive decline and are increasingly recognized as key contributors to the pathogenesis of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD)...

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BACKGROUND: Gout is a chronic inflammatory diseases caused by monosodium urate crystal deposition. However, the role of interleukin (IL)-36 in gout has not dbeen elucidated. METHODS: We enrolled 75 subjects, including 20 healthy controls (HC), 30 patients with acute gout attack and 25 patients in remission. Baseline data were obtained through clinical interrogation and laboratory data were obtained through tests of blood samples. Serum levels of IL-36α were detected using enzyme-linked immunosorbent assay...

Previously, we demonstrated that linear peptide epoxyketones targeting the immunoproteasome (iP) could ameliorate cognitive deficits in mouse models of Alzheimer's disease (AD) independently of amyloid deposition. We also reported the first iP-targeting macrocyclic peptide epoxyketones, which exhibit improved metabolic stability compared with their linear counterparts. Here, we prepared additional macrocyclic peptide epoxyketones and compared them with existing macrocyclic iP inhibitors by assessing Caco2 cell-based permeability and microsomal stability, providing the four best macrocyclic iP inhibitors...

Glial fibrillary acidic protein (GFAP), a proxy of astrocyte reactivity, has been proposed as biomarker of Alzheimer's disease. However, there is limited information about the correlation between blood biomarkers and post-mortem neuropathology. In a single-centre prospective clinicopathological cohort of 139 dementia patients, for which the time-frame between GFAP level determination and neuropathological assessment was exceptionally short (on average 139 days), we analysed this biomarker, measured at three time points, in relation to proxies of disease progression such as cognitive decline and brain weight...

Recent development of amyloid-β (Aβ)-targeted immunotherapies for Alzheimer's disease (AD) have highlighted the need for accurate diagnostic methods. Antibody-based positron emission tomography (PET) ligands are well suited for this purpose as they can be directed toward the same target as the therapeutic antibody. Bispecific, brain-penetrating antibodies can achieve sufficient brain concentrations, but their slow blood clearance remains a challenge, since it prolongs the time required to achieve a target-specific PET signal...

BACKGROUND: Musculoskeletal injuries (MSI) are common in racehorses and have been of increasing concern in horses travelling internationally to compete. Understanding the differences in bone turnover between local horses and international horses following long-distance air transportation may inform MSI prevention strategies. OBJECTIVES: To understand the differences in bone turnover markers and risk of MSI between local horses and international horses following long-distance air transportation...

BACKGROUND: Mastitis in goats is unquestionably a grave concern, with far-reaching implications for both animal well-being and productivity, while also presenting a potential threat to public health. AIM: The study aimed to compare culture methods and multiplex PCR (m-PCR) in the detection of the most three common mastitis-causing pathogens ( Staphylococcus aureus , Escherichia coli , and Streptococcus spp.) and investigate the gene expression, single nucleotide polymorphisms (SNPs), serum concentrations of immunological and antioxidant indicators linked to mastitis in Shami goats...

BACKGROUND AND OBJECTIVES: Elevated levels of Alzheimer disease (AD) blood-based biomarkers are associated with accelerated cognitive decline. However, their distinct relationships with specific cognitive and functional domains require further investigation. We aimed at estimating the associations between AD blood-based biomarkers and the trajectories of distinct cognitive and functional domains over a 5-year follow-up period. METHODS: We conducted a clinic-based prospective study using data from the MEMENTO study, a nationwide French cohort...

BACKGROUND: Kinetic modeling of 18 F-florbetaben provides important quantification of brain amyloid deposition in research and clinical settings but its use is limited by the requirement of arterial blood data for quantitative PET. The total-body EXPLORER PET scanner supports the dynamic acquisition of a full human body simultaneously and permits noninvasive image-derived input functions (IDIFs) as an alternative to arterial blood sampling. This study quantified brain amyloid burden with kinetic modeling, leveraging dynamic 18 F-florbetaben PET in aorta IDIFs and the brain in an elderly cohort...

The blood-brain barrier (BBB) is instrumental in clearing toxic metabolites from the brain, such as amyloid-β (Aβ) peptides, and in delivering essential nutrients to the brain, like insulin. In Alzheimer's disease (AD) brain, increased Aβ levels are paralleled by decreased insulin levels, which are accompanied by insulin signaling deficits at the BBB. Thus, we investigated the impact of insulin-like growth factor and insulin receptor (IGF1R and IR) signaling on Aβ and insulin trafficking at the BBB...

OBJECTIVE: Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood. METHODS: We acquired simultaneous polysomnography and all-night blood sampling in 60 healthy volunteers aged 20-68 years...

INTRODUCTION: A major limitation in Alzheimer's disease (AD) research is the lack of the ability to measure cognitive performance at scale-robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD. METHODS: We used a novel web-based platform that assessed different cognitive functions in AD patients ( N  = 46) and elderly controls ( N  = 53) who were also evaluated for plasma biomarkers (amyloid beta 42/40 ratio, phosphorylated tau ([p-tau]181, glial fibrillary acidic protein, neurofilament light chain)...

Down syndrome (DS) is caused by a third copy of chromosome 21. Alzheimer's disease (AD) is a neurodegenerative condition characterized by the deposition of amyloid-beta (Aβ) plaques and neurofibrillary tangles in the brain. Both disorders have elevated Aβ, tau, dysregulated immune response, and inflammation. In people with DS, Hsa21 genes like APP and DYRK1A are overexpressed, causing an accumulation of amyloid and neurofibrillary tangles, and potentially contributing to an increased risk of AD...