B-rich colistin and B-pure colistin as novel strategies to increase the therapeutic window of polymyxin antibiotic therapy.

The rise of multidrug-resistant bacteria has made necessary the reintroduction of legacy antibiotics, such as colistin, only used as last-resort due to its concerning derived nephro- and neuro-toxicities. This lipopeptide antibiotic is primarily composed of two main components, colistin A and colistin B. However, their individual toxicological profiles remain poorly understood.

Protein-based Diagnosis and Analysis of Co-pathologies Across Neurodegenerative Diseases: Large-Scale AI-Boosted CSF and Plasma Classification.

Neurodegenerative diseases (including Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Dementia with Lewy bodies) pose diagnostic challenges due to overlapping pathology and clinical heterogeneity. We leveraged proteomic data from more than 21,000 cerebrospinal fluid and plasma samples to develop and validate explainable, boosting-based multi-disease AI classifiers. The models achieved weighted AUCs in the testing datasets of 0.

Colistin-loaded biodegradable nanoparticles as a promising antibacterial medication to reduce colistin-induced toxicity.

Infectious diseases cause mortality rates over 17 million people per year. Among them, bacterial infections are one of the major causes. Nosocomial infections, including pneumonia and blood stream infections, are some of the most severe bacterial diseases and many of them display antimicrobial resistance.

Protein-based Diagnosis and Analysis of Co-pathologies Across Neurodegenerative Diseases: Large-Scale AI-Boosted CSF and Plasma Classification.

Neurodegenerative diseases (including Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Dementia with Lewy bodies) pose diagnostic challenges due to overlapping pathology and clinical heterogeneity. We leveraged proteomic data from more than 21,000 cerebrospinal fluid and plasma samples to develop and validate explainable, boosting-based multi-disease AI classifiers. The models achieved weighted AUCs in the testing datasets of 0.

GWAS meta-analysis of CSF Alzheimer's disease biomarkers 18,948 individuals reveal novel loci and genes regulating lipid metabolism, brain volume and autophagy.

Cerebrospinal fluid (CSF) amyloid beta (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau181) are well accepted markers of Alzheimer's disease. We performed a GWAS meta-analysis including 18,948 individuals of European and 416 non-European ancestry. We identified 12 genome-wide significant loci across all three biomarkers, eight of them novel.

Large-scale plasma proteomic profiling unveils diagnostic biomarkers and pathways for Alzheimer's disease.

Proteomic studies have been instrumental in identifying brain, cerebrospinal fluid and plasma proteins associated with Alzheimer's disease (AD). Here, we comprehensively examined 6,905 aptamers corresponding to 6,106 unique proteins in plasma in more than 3,300 well-characterized individuals to identify new proteins, pathways and predictive models for AD. We identified 416 proteins (294 new) associated with clinical AD status and validated the findings in two external datasets representing more than 7,000 samples.

A Spanish-Portuguese GWAS of progressive supranuclear palsy reveals a novel risk locus in NFASC.

Progressive supranuclear palsy (PSP) is a rare 4-repeat tauopathy that causes behavioural, movement and cognitive abnormalities. We genotyped all available clinical and histopathological PSP cases in Spain and Portugal (N = 522), and conducted the largest PSP GWAS of the Iberian population to date. Genetic burden analysis revealed reduced diagnostic specificity in clinically diagnosed atypical PSP cases-when applying the 2017 MDS criteria-compared to Richardson's syndrome cases.

Kratopenia as an indicator of sarcopenia in smokers: Cut-off points for peak knee torque.

Muscle strength is a crucial predictor of adverse outcomes and is essential for identifying kratopenia and physical limitations. Smoking can aggravate this condition, damaging the musculoskeletal system. Assessing muscle strength, especially with portable dynamometers, is essential for early detection of muscle dysfunction.

APOE Haplotype Phasing Using ONT Long-Read Sequencing Reveals Two Common ε3 and ε4 intragenic haplotypes in the Spanish Population.

Background: The apolipoprotein E () gene is a key genetic determinant of Alzheimer's disease (AD) risk, with the ε4 allele significantly increasing susceptibility. While the pathogenic effects of the ε4 allele are well established, the functional impact of distinct haplotype configurations within the broader ε3 and ε4 backgrounds remains poorly understood. This study investigates the role of intragenic sub haplotypes in modulating expression and their potential influence on AD progression.

Large-scale Plasma Proteomic Profiling Unveils Novel Diagnostic Biomarkers and Pathways for Alzheimer's Disease.

Alzheimer disease (AD) is a complex neurodegenerative disorder. Proteomic studies have been instrumental in identifying AD-related proteins present in the brain, cerebrospinal fluid, and plasma. This study comprehensively examined 6,905 plasma proteins in more than 3,300 well-characterized individuals to identify new proteins, pathways, and predictive model for AD.

Linking genomic and proteomic signatures to brain amyloid burden: insights from GR@ACE/DEGESCO.

Alzheimer's disease (AD) is a complex disease with a strong genetic component, yet many genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may provide insights into the underlying biology of the disease. We performed a meta-GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n = 2,076).

Licochalcone A prevents cognitive decline in a lipopolysaccharide-induced neuroinflammation mice model.

Inflammation plays a key role in the development of neurodegenerative disorders that are currently incurable. Licochalcone A (LCA) has been described as an emerging anti-inflammatory drug with multiple therapeutical properties that could potentially prevent neurodegeneration. However, its neuroprotective mechanism remains unclear.

Colistin treatment causes neuronal loss and cognitive impairment via ros accumulation and neuronal plasticity alterations.

The rise of antimicrobial resistance has made necessary the increase of the antibacterial arsenal against multidrug-resistant bacteria. In this context, colistin has re-emerged as a first-line antibiotic in critical situations despite its nephro- and neuro- toxicity at peripheral level. However, the mechanism underlying its toxicity remains unknown, particularly in relation to the central nervous system (CNS).

Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort.

High-throughput proteomic platforms are crucial to identify novel Alzheimer's disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan 7k) and antibody-based (Olink Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan assays analyzing the same samples, and between SomaScan and Olink results.

Associations of plasma SMOC1 and soluble IL6RA levels with the progression from mild cognitive impairment to dementia.

Despite the central role attributed to neuroinflammation in the etiology and pathobiology of Alzheimer's disease (AD), the direct link between levels of inflammatory mediators in blood and cerebrospinal fluid (CSF) compartments, as well as their potential implications for AD diagnosis and progression, remains inconclusive. Moreover, there is debate on whether inflammation has a protective or detrimental effect on disease onset and progression. Indeed, distinct immunological mechanisms may govern protective and damaging effects at early and late stages, respectively.

Changes in choroidal thickness quantified by Optical Coherence Tomography across cognitive impairment: data from the NORFACE cohort.

Background: Optical coherence tomography (OCT) enables high-resolution imaging of ocular structures in health and disease. Choroid thickness (CT) is a key vascular retinal parameter that can be assessed by OCT and might be relevant in the evaluation of the vascular component of cognitive decline. We aimed to investigate CT changes in a large cohort of individuals cognitive unimpaired (CU), with mild cognitive impairment due to Alzheimer's (MCI-AD), mild cognitive impairment due to cerebrovascular disease (MCI-Va), Alzheimer's disease dementia (ADD), and vascular dementia (VaD).

Amyloid deposition in adults with drug-resistant temporal lobe epilepsy.

Objective: Pathological amyloid-β (Aβ) accumulation and hyperphosphorylated tau proteins have been described in resected temporal lobe specimens of epilepsy patients. We aimed to determine cerebrospinal fluid (CSF) Aβ1-42 and p181-tau levels and cerebral Aβ deposits on positron emission tomography (Aβ PET) and correlate these findings with cognitive performance in adults with drug-resistant temporal lobe epilepsy (TLE).

Methods: In this cross-sectional study, we enrolled individuals with drug-resistant TLE who were 25-55 years old.

Clinical value of plasma pTau181 to predict Alzheimer's disease pathology in a large real-world cohort of a memory clinic.

Background: The identification of patients with an elevated risk of developing Alzheimer's disease (AD) dementia and eligible for the disease-modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed to translate them to clinical practice. Here we evaluated the clinical applicability of plasma pTau181 as a predictive marker of AD pathology in a large real-world cohort of a memory clinic.

Connecting genomic and proteomic signatures of amyloid burden in the brain.

Background: Alzheimer's disease (AD) has a high heritable component characteristic of complex diseases, yet many of the genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may be helpful to understand the underlying biology of the disease.

Methods: We performed a meta-analysis of GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n=2,076).

The Interplay of Astrocytes and Neurons in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) comprises a complex neurodevelopmental condition characterized by an impairment in social interaction, involving communication deficits and specific patterns of behaviors, like repetitive behaviors. ASD is clinically diagnosed and usually takes time, typically occurring not before four years of age. Genetic mutations affecting synaptic transmission, such as neuroligin and neurexin, are associated with ASD and contribute to behavioral and cognitive deficits.

Association of oxidative stress and inflammatory metabolites with Alzheimer's disease cerebrospinal fluid biomarkers in mild cognitive impairment.

Background: Isoprostanes and prostaglandins are biomarkers for oxidative stress and inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify the association of isoprostanes and prostaglandins with the Amyloid, Tau, Neurodegeneration (ATN) biomarkers (Aβ-42, p-tau, and t-tau) of AD pathophysiology in mild cognitive impairment (MCI) subjects.