Social Risks and Nonadherence to Recommended Cancer Screening Among US Adults.

Importance: Research indicates that social drivers of health are associated with cancer screening adherence, although the exact magnitude of these associations remains unclear.

Objective: To investigate the associations between individual-level social risks and nonadherence to guideline-recommended cancer screenings.

Design, Setting, And Participants: This cross-sectional study used 2022 Behavioral Risk Factor Surveillance System data from 39 US states and Washington, DC.

Factors in Initial Anticoagulation Choice in Hospitalized Patients With Pulmonary Embolism.

Importance: Despite guideline recommendations to use low-molecular-weight heparins (LMWHs) or direct oral anticoagulants in the treatment of most patients with acute pulmonary embolism (PE), US-based studies have found increasing use of unfractionated heparin (UFH) in hospitalized patients.

Objective: To identify barriers and facilitators of guideline-concordant anticoagulation in patients hospitalized with acute PE.

Design, Setting, And Participants: This qualitative study conducted semistructured interviews from February 1 to June 3, 2024, that were recorded, transcribed, and analyzed in an iterative process using reflexive thematic analysis.

Escape of Kdm6a from X Chromosome Is Detrimental to Ischemic Brains via IRF5 Signaling.

The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our previous study has suggested that the X escapee genes Kdm6a and Kdm5c are involved in microglial activation after stroke in aged mice.

The economic burden of diabetes in spinal fusion surgery: a systematic review and meta-analysis.

Purpose: This study aimed at comparing the costs of spinal fusion surgery between patients with and without diabetes.

Methods: Following PRISMA guidelines, a systematic search of four databases was conducted. A meta-analysis was performed on comparative studies examining diabetic versus non-diabetic adults undergoing cervical/lumbar fusion in terms of cost.

Basic Science and Pathogenesis.

Background: Numerous studies have highlighted the role of oxidative stress in Alzheimer's disease (AD) development. Yet, the alignment of systemic and central oxidative stress biomarkers is unclear across diverse populations in the AD continuum. This study aims to assess protein damage levels in plasma and cerebrospinal fluid (CSF) within the AD continuum.

Basic Science and Pathogenesis.

Background: As humans age, some experience cognitive impairment while others do not. When impairment occurs, it varies in severity across individuals. Translationally relevant models are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brain's susceptibility to aging.

Basic Science and Pathogenesis.

Background: The misfolding and aggregation of the tau protein into neurofibrillary tangles constitute a central feature of tauopathies. Traumatic brain injury (TBI) has emerged as a potential risk factor, triggering the onset and progression of tauopathies. Our previous research revealed distinct polymorphisms in soluble tau oligomers originating from single versus repetitive mild TBIs.

Basic Science and Pathogenesis.

Background: Non-coding RNA species, such as microRNA (miRNA), regulate multiple biological and pathological processes by binding to target mRNAs and facilitating alteration of translation levels via complexes such as RNA-induced silencing complex (RISC). Disrupting this process could contribute to AD pathogenesis by fostering aggregation of hyperphosphorylated microtubule-associated protein tau and amyloid-β (Aβ) peptides, and neuroinflammation. Understanding how these pathological changes are regulated remains our research focus.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) has a complex etiology where insults in multiple pathways conspire to disrupt neuronal function, yet molecular changes underlying AD remain poorly understood. Previously, we performed mass-spectrometry on post-mortem human brain tissue to identify >40 protein co-expression modules correlated to AD pathological and clinical traits. Module 42 has the strongest correlation to AD pathology and consists of 32 proteins including SMOC1, a predicted driver of network behavior and potential biomarker for AD.

Basic Science and Pathogenesis.

Background: Mitochondria are organelles where energy production takes place via oxidative phosphorylation, thus mitochondrial function influences the organs with large energy consumption, such as the brain. Mitochondria contain their own circular genome (mtDNA), which encodes essential proteins/RNAs involved in oxidative phosphorylation. The maternal inheritance of mtDNA, combined with a higher risk of Alzheimer's disease (AD) observed in females, suggest mtDNA may have a role in AD.

Basic Science and Pathogenesis.

Background: Neurodegeneration is characterized by the progressive loss of neurons. However, the mechanisms by which neurons die in Alzheimer's disease (AD) remain elusive. Disrupted iron homeostasis is associated with accelerated cognitive decline, amyloid beta deposition, and AD progression, but its pathogenic relevance is poorly understood.

Basic Science and Pathogenesis.

Background: Imbalanced Fe levels can lead to oxidative stress and initiate ferroptosis, an Fe-dependent cell death that involves lipid peroxidation and can lead to neuron cell loss in neurodegenerative diseases including Alzheimer's disease (AD). While the Fe/Fe ratio has been identified as the primary determining factor for lipid peroxidation, the role of Fe redox equilibrium and dynamic in AD is not well understood, due to limited tools for visualizing Fe and Fe simultaneously. To overcome this limitation, we recently reported DNAzyme-based sensors for simultaneous imaging of Fe and Fe.

Basic Science and Pathogenesis.

Background: Alzheimer's Disease (AD) incidence is almost double in female than male, suggesting sex-specific AD risk genes remain unknown.

Method: We designed a statistical physics approach that exploits freely available but massive evolutionary and phylogenetic coupling data on sequence variation and speciation. These couplings lead to quantifiable values for the selection pressure exerted on the genes within a population.

Basic Science and Pathogenesis.

Background: An increasing body of evidence has suggested that the pathogenesis of Alzheimer's disease (AD) is not confined to the neurons but instead that neuroinflammation plays a significant role in the disease, with an interplay between the brain and the immune system. So far, their shared genetic components have not been systematically studied.

Method: We investigated the shared genetic architecture between AD and a plethora of immune-mediated diseases using the genome-wide association studies (GWAS) summary statistics data: allergic rhinitis, asthma, atopic dermatitis, celiac disease, Crohn's disease, hypothyroidism, primary sclerosing cholangitis, RA, systemic lupus erythematosus, ulcerative colitis, and vitiligo.

Basic Science and Pathogenesis.

Background: An important hallmark of Alzheimer's Disease (AD) is the presence of neurofibrillary tangles (NFTs) composed of phosphorylated tau, which are commonly assessed using AT8 immunostains. Identifying additional markers to characterize the spectrum of NFT pathology is crucial for advancing our understanding and diagnosis of AD. This study introduces new potential markers to differentiate between tangles and healthy neurons.

Basic Science and Pathogenesis.

Background: SNX19 is a key player in endolysosomal and autophagy pathways, which have been extensively reported in neuronal dysfunction and neurodegenerative diseases. Although genetic and cellular evidence suggests SNX19 contributes to neuropathology, the underlying mechanisms remain unknown. Here, we propose to study the mechanism in aging postmortem brain tissue at single cell level and model SNX19 in human induced pluripotent stem cell (hiPSCs) derived brain organoids.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a severe neurodegenerative condition that affects millions of people worldwide. The TgF344 AD rat model, which exhibits early depression-like behavior followed by later cognitive impairment, is widely used to evaluate putative biomarkers and potential treatments for AD. The P7C3 neuroprotective compounds have shown protective efficacy for both brain pathology and neuropsychiatric impairment in this model.

Basic Science and Pathogenesis.

Background: Genetic variants that confer protection from Alzheimer's disease (AD) may be particularly critical in developing therapeutics. To target protective variant identification, we performed genetic association testing among selected individuals with whole genome sequencing (WGS) that remained alive and dementia-free beyond age 85 ("Wellderly").

Methods: We selected 1,873 White and Black Wellderly individuals with documented normal cognition beyond age 85 as determined by direct, in-person assessment with WGS from the NHLBI TOPMed project.

Basic Science and Pathogenesis.

Background: Rodent models have been proved pivotal in Alzheimer's disease (AD) research. Nevertheless, the use of models that only recapitulate one aspect of AD neuropathology, and of early time points that might be excluding important features such as age-dependent inflammation and senescence, could hinder the development of effective AD therapeutics. Several tau immunotherapies are currently undergoing clinical trial.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is characterized by progressive, irreversible neurodegeneration, leading to memory loss and cognitive decline. In mouse models of AD, global decreases in cerebral blood flow (CBF) are brought on by the plugging of capillaries by arrested neutrophils, and the administration of the neutrophil-specific antibody against Ly6G (anti-Ly6G) reduces these capillary stalls in minutes and improves cognitive function within hours. This suggests that at least some aspects of neural activity impairment are reversible, but the mechanism of this recovery - and what specific neural activity is normalized - is not yet known.

Basic Science and Pathogenesis.

Background: Mitochondria plays a crucial role at synapses in providing synaptic energy, healthy synaptic function, and cognitive functions. Amyloid-beta and phosphorylated tau protein oligomers cause severe mitochondrial defects in Alzheimer's disease (AD), which leads to the lack of synaptic energy and impaired synapse functions in AD. MicroRNAs (miRNAs) present within the mitochondria are involved in multiple mitochondrial activities and mitochondrial function.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) and other dementia risk may be influenced by the immune function and associated with several white blood cell type counts. In cognitively normal Black, Hispanic, and non-Hispanic white older adults we related three white blood cell types previously associated with AD risk to tau positron emission tomography (PET) values in the medial temporal lobe (MTL), where tau accumulates early. We assessed whether amyloid positivity moderated this relationship.

Basic Science and Pathogenesis.

Background: In Alzheimer's disease (AD), histone acetylation is disrupted, suggesting loss of transcriptional control. Moreover, converging evidence suggests an age- and AD-dependent loss of transcription controlled by all-trans-retinoic acid (ATRA), the bioactive metabolite of vitamin A (VA). Antioxidant depletion causes oxidative stress (OS).

Basic Science and Pathogenesis.

Background: Tauopathies, including Alzheimer's Disease and Frontotemporal Dementia, are characterized as intracellular lesions composed of aggregated tau proteins. Soluble tau oligomers are shown to be one of the most toxic species and are responsible for the spread of tau pathology. Recent studies have found that several proteins such as amyloid b, a-synuclein, and TDP-43 can aggregate tau.

Basic Science and Pathogenesis.

Background: Disrupted balance between amyloidogenic and non-amyloidogenic pathways leads to cognitive decline in Alzheimer's disease (AD). Evidence suggests vitamin A (VA) supplementation favors the non-amyloidogenic pathway through upregulation of α-secretase. Originally used to map embryonic retinoic acid (RA) signaling, RARE-LacZ mice possess multiple LacZ genes controlled by retinoic acid response elements (RAREs).