Alzheimers disease

BACKGROUND: As global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture relationships central to the disease's etiology and response to drugs. OBJECTIVE: We designed the Alzheimer's Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics...

The claustrum is an irregular and fine sheet of grey matter in the basolateral telencephalon present in almost all mammals. The claustrum has been the object of several studies using animal models and, more recently, in human beings using neuroimaging. One of the most extended cognitive processes attributed to the claustrum is the salience process, which is also related to the insular cortex. In the same way, studies with human subjects and functional magnetic resonance imaging have reported the coactivation of the claustrum/insular cortex in the integration of sensory signals...

BACKGROUND: The Apolipoprotein E (APOE) gene has been established in the Alzheimer's disease (AD) literature to impact brain structure and function and may also show congruent effects in healthy older adults, although findings in this population are much less consistent. The current study aimed to replicate and expand the multimodal approach employed by Honea et al. Structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and neuropsychological measures were used to investigate the impact of APOE-ε status on grey matter structure, white matter integrity, and cognitive functioning...

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...

STUDY OBJECTIVES: Apolipoprotein E ɛ4 (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD). In addition, APOE4 carriers may exhibit sleep disturbances, but conflicting results have been reported, such that there is no clear consensus regarding which aspects of sleep are impacted. Our objective was to compare objective sleep architecture between APOE4 carriers and non-carriers, and to investigate the modulating impact of age, sex, cognitive status and obstructive sleep apnea...

BACKGROUND: The causal association between particulate matter 2.5 (PM2.5) and Alzheimer's disease (AD) remains inconclusive, and the mediators of the association have yet to be explored. AIMS: We aimed to assess the potential causal relationship between PM2.5 and AD, and to investigate the mediating role of dehydroepiandrosterone sulphate (DHEAS). SUBJECTS AND METHODS: We implemented a two-sample Mendelian randomisation (MR) study to examine the genetic predisposition to PM2...

Intraperitoneal dissemination is the main method of epithelial ovarian cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14-3-3 proteins to act as a chaperone molecule and has a limited positive effect on 14-3-3 protein stability...

BACKGROUND: Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD. METHODS: Genome-wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age-matched controls, and 346 cognitively healthy centenarians...

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...

OBJECTIVE: To analyze the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) on the cognitive function of individuals with Alzheimer's disease (AD). METHODS: This systematic review with meta-analysis and meta-regression included randomized clinical trials published until 05/2022. We included studies conducted with individuals with AD of both sexes, aged between 55 and 85 years, treated with tDCS, TMS, or both...

INTRODUCTION: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD). METHODS: Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18 F]SynVesT-1 and [18 F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability...

Alzheimer's disease (AD), one of the main causes of dementia, is a neurodegenerative disorder. Cholinesterase inhibitors are used in the treatment of AD, but prolonged use of these drugs can lead to serious side effects. Drug repurposing is an approach that aims to reveal the effectiveness of drugs in different diseases beyond their clinical uses. In this work, we investigated in vitro and in silico inhibitory effects of 11 different drugs on cholinesterases. The results showed that trimebutine, theophylline, and levamisole had the highest acetylcholinesterase inhibitory actions among the tested drugs, and these drugs inhibited by 68...

AIMS: Hirano bodies (HBs) are eosinophilic pathological structures with two morphological phenotypes commonly found in the hippocampal CA1 region in Alzheimer's disease (AD). This study evaluated the prevalence and distribution of HBs in AD and other neurodegenerative diseases. METHODS: This cross-sectional study systematically evaluated HBs in a cohort of 193 cases with major neurodegenerative diseases, including AD (n = 91), Lewy body disease (LBD, n = 87), progressive supranuclear palsy (PSP, n = 36), multiple system atrophy (MSA, n = 14) and controls (n = 26)...

The intricate parallels in structure and function between the human retina and the central nervous system designate the retina as a prospective avenue for understanding brain-related processes. This review extensively explores the shared physiopathological mechanisms connecting age-related macular degeneration (AMD) and proteinopathies, with a specific focus on tauopathies. The pivotal involvement of oxidative stress and cellular senescence emerges as key drivers of pathogenesis in both conditions. Uncovering these shared elements not only has the potential to enhance our understanding of intricate neurodegenerative diseases but also sets the stage for pioneering therapeutic approaches in AMD...

The efficacy of current treatments is still insufficient for Alzheimer's disease (AD), the most common cause of Dementia. Out of the two pathological hallmarks of AD amyloid-β plaques and neurofibrillary tangles, comprising of tau protein, tau pathology strongly correlates with the symptoms of AD. Previously, screening for inhibitors of tau aggregation that target recombinant tau aggregates have been attempted. Since a recent cryo-EM analysis revealed distinct differences in the folding patterns of heparin-induced recombinant tau filaments and AD tau filaments, this study focused on AD seed-dependent tau aggregation in drug repositioning for AD...

OBJECTIVE: This study aims to explore the relationship between physical activity (PA) and postoperative delirium (POD). METHODS: We selected 400 patients from the Perioperative Neurocognitive Disorder and Biomarkers Lifestyle (PNDABLE) database, and the patients in the PNDABLE database were sampled and tested Alzheimer's biomarkers. The diagnosis of POD was made using the Confusion Assessment Scale (CAM) and the severity was assessed using Memorial Delirium Assessment Scale (MDAS)...

Brain state classification by applying deep learning techniques on neuroimaging data has become a recent topic of research. However, unlike domains where the data is low dimensional or there are large number of available training samples, neuroimaging data is high dimensional and has few training samples. To tackle these issues, we present a sparse feedforward deep neural architecture for encoding and decoding the structural connectome of the human brain. We use a sparsely connected element-wise multiplication as the first hidden layer and a fixed transform layer as the output layer...

INTRODUCTION: Awareness influences the evolution of neurodegenerative dementias. We gathered participants' and caregivers assessments of dependence in daily activities and we studied how each score would be related to next year participant autonomy, independently of other explicative variables. METHOD: We retrospectively analyzed data from mildly demented participants with a clinical diagnosis of Alzheimer's disease (AD, n = 186) and frontotemporal dementia (FTD, n = 29) and their relatives...

BACKGROUND: Tremendous research efforts have been made in the Alzheimer's disease (AD) field to understand the disease etiology, progression and discover treatments for AD. Many mechanistic hypotheses, therapeutic targets and treatment strategies have been proposed in the last few decades. Reviewing previous work and staying current on this ever-growing body of AD publications is an essential yet difficult task for AD researchers. METHODS: In this study, we designed and implemented a natural language processing (NLP) pipeline to extract gene-specific neurodegenerative disease (ND) -focused information from the PubMed database...

BACKGROUND: Using in vivo neuroimaging techniques, growing evidence has demonstrated that the choroid plexus (CP) volume is enlarged in patients with several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. However, although animal and postmortem findings suggest that CP abnormalities are likely important pathological mechanisms underlying amyotrophic lateral sclerosis (ALS), the third most common neurodegenerative disease, no available study has been conducted to thoroughly assess CP abnormalities and their clinical relevance in vivo in ALS patients to date...