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.

The Age-Old Question in Nipple-Sparing Mastectomy: Is Older Age a Contraindication?

Background: Nipple-sparing mastectomy (NSM) is infrequently performed in older women, at least in part owing to concerns regarding age-related complications. We describe postoperative outcomes of NSM in older women and risk factors for complications, with the goal of informing patient selection and decision-making.

Patients And Methods: Cases of NSM with immediate implant-based reconstruction were identified from an institutional database (2009-2019).

Thermogelation of nanoemulsions stabilized by a commercial pea protein isolate: high-pressure homogenization defines gel strength.

The impact of animal-based food production on climate change drives the development of plant-based alternatives. We demonstrate the use of colloidal thermogelation on a real nanoemulsion system to create structured gels that could be of interest for thermo-mechanical processing of next-generation plant-based food applications. We use a commercial pea protein isolate (PPI) without further purification to stabilize a 20 vol% peanut oil-in-water nanoemulsion at pH = 7 by high-pressure homogenization (HPH) and demonstrate the temperature induced gelation behavior of the nanoemulsion as a function of the HPH processing parameters.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) in Alzheimer's disease (AD) leveraging endophenotypes beyond case/control diagnosis, such as brain amyloid β pathology, have shown promise in identifying novel variants and understanding their potential functional impact. In this study, we leverage two brain amyloid β pathology measurement modalities, PET imaging and neuropathology, to address sample size limitations and to discover novel genetic drivers of disease.

Method: We conducted a meta-analysis on an amyloid PET imaging GWAS (N = 7,036, 35% amyloid positive, 53.

Basic Science and Pathogenesis.

Background: We aim to investigate efficacies of Ras homolog (Rho)-associated kinases (ROCK) inhibitors on Alzheimer's disease (AD) pathological proteins in human induced pluripotent stem cell (iPSC)-differentiated human neurons and the P301S tau transgenic mouse model (PS19).

Method: Quantitative liquid chromatography-mass spectrometry (LC-MS/MS) and targeted ELISA were implemented to investigate the effect of treatment with fasudil or its derivatives on the human neurons and brains from PS19 mice. We explored the efficacy of these ROCK inhibitors in reducing tau phosphorylation, and the brain proteomic profiles after their administration in mice.

Basic Science and Pathogenesis.

Background: In tauopathies, the protein tau misfolds into a b-sheet conformation that self-templates and spreads throughout the brain causing progressive degeneration. Biological and structural data have shown that the shape, or strain, that tau adopts when it misfolds determines which disease a patient will develop. We previously used HEK293T cells expressing TauRD-YFP to show that tau strain formation is isoform-specific.

Basic Science and Pathogenesis.

Background: Women are disproportionately affected by Alzheimer's disease (AD) and exhibit greater AD neuropathology than men. Women possess two X chromosomes, with one randomly silenced across each cell for dosage compensation. X chromosome inactivation (XCI) is not complete, and XCI-escaping genes provide a promising avenue of discovery for biological pathways driving sex-specific AD risk.

Basic Science and Pathogenesis.

Background: A significant proportion of individuals preserve cognitive function despite meeting neuropathological criteria for Alzheimer's disease (AD) at autopsy, known as cognitive resilience. We aimed to define the molecular and cellular signatures of cognitive resilience against AD.

Method: We integrated multi-modal data from the Religious Order Study and Memory and Aging Project (ROSMAP), including bulk (n = 631) and multi-regional single nucleus (n = 48) RNA sequencing.

Basic Science and Pathogenesis.

Background: Some individuals can tolerate the presence of Alzheimer disease neuropathologic changes (ADNC) (e.g., plaques and tangles) without developing dementia.

Basic Science and Pathogenesis.

Background: Cerebral small vessel disease (CSVD), which includes cerebral amyloid angiopathy (CAA) and arteriolosclerosis, often co-occurs with Alzheimer's disease (AD) pathology. The medial temporal lobe (MTL) is susceptible to hosting multiple AD pathologies, such as neurofibrillary tangles (NFTs), amyloid-β plaques, phospho-Tar-DNA-Binding-Protein-43 (pTDP-43), as well as CSVD. Whether a causal relationship between these pathologies exists remains largely unknown, but one potential linking mechanism is the dysfunction of perivascular clearance.

Basic Science and Pathogenesis.

Background: In cerebral amyloid angiopathy, amyloid beta accumulates within the walls of blood vessels and contributes to impaired vascular integrity and function. In this work, we observe that tau protein similarly builds up along blood vessels in Alzheimer's disease brain.

Method: We obtained frozen inferior temporal cortex from the Massachusetts Alzheimer's Disease Research Center from n = 7 neuropathological confirmed Alzheimer's disease donors and n = 6 normal aging controls.

Basic Science and Pathogenesis.

Background: Angiotensin-converting enzyme (ACE) is a validated risk locus for developing late-onset Alzheimer's disease (LOAD). ACE1 controls blood pressure through the renin-angiotensin system (RAS), but it is also present and acts locally in the brain. Hypertension is associated with an increased risk for developing AD, and people taking select RAS-targeting therapeutics have reduced incidence of AD.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the deposition of amyloid-beta and hyperphosphorylated tau (P-tau) proteins in the brain. P-tau accumulates in neurons and is strongly associated with AD severity and affected brain regions. However, only a subset of neurons in AD exhibit tau pathology.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the most common type of dementia which results in debilitating memory loss as the disease advances. However, among older adults with AD, some may experience rapid cognitive decline while others may maintain a stable cognitive status for years. In addition to the amyloid plaques, tau tangles, and neuronal inflammation characteristic of AD, there is strong evidence of dysregulation in the peripheral immune system, including decreased naïve T cells and increased memory T cells among older adults with AD.

Basic Science and Pathogenesis.

Background: Spouses of Alzheimer's disease (AD) patients are at a higher risk of developing incidental dementia. However, the causes and underlying mechanism of this clinical observation remain largely unknown. One possible explanation is linked to microbiota dysbiosis, a condition that has been associated with AD.

Basic Science and Pathogenesis.

Background: In Alzheimer's disease (AD), the spread of Tau proteopathic seeds across the cerebral cortex parallels the disease progression. Previously, it was shown that isolating high-molecular-weight (HMW) Tau species via size exclusion chromatography (SEC) from human brain lysate of AD patients resulted in the enrichment of Tau aggregation-prone species. However, whether the HMW Tau population contain a homogenous or heterogeneous mixture of Tau species is still unknown.

Basic Science and Pathogenesis.

Background: Down syndrome (DS) is characterized by the overexpression of the amyloid precursor protein gene (APP) and pro-inflammatory genes, leading to progressive beta-amyloid (Aβ) accumulation. This accumulation in DS may exacerbate neuroinflammation, contributing to the pathogenesis of Alzheimer's Disease (AD). Experimental models suggest that aquaporin 4 (AQP4), an astrocytic water channel implicated in Aβ clearance, is mislocalized with increased Aβ burden.

Basic Science and Pathogenesis.

Background: Currently, it is unclear to what extent late-onset Alzheimer's disease (AD) risk variants contribute to early-onset AD (EOAD). One method to clarify the contribution of late-onset AD genetic risk to EOAD is to investigate the association of AD polygenic risk scores (PRS) with EOAD. We hypothesize that in the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS), EOAD participants will have greater PRS than early-onset amyloid-negative cognitively-impaired participants (EOnonAD) and controls, and investigate the association of AD PRS with age of disease onset (AoO) and cognitive performance.

Basic Science and Pathogenesis.

Background: Structural variants (SVs), genomic alterations exceeding 50 base-pairs, are known for their significant impact on disease pathology. However, the role of SVs in Alzheimer's Disease (AD) remains unclear. Using a novel high-accuracy SV calling pipeline, we analyzed a diverse sample from the Alzheimer's Disease Sequencing Project (ADSP).

Basic Science and Pathogenesis.

Two broad classes of mechanisms have emerged for understanding the Amyloid-Related Imaging Abnormalities (ARIA) associated with anti-beta-amyloid immunotherapy. One set of mechanisms proposes that ARIA is driven by large-scale transfer of antibody-bound amyloid from brain parenchyma to the perivascular and vascular compartments. This class of mechanisms is indirectly supported by neuropathological evidence that immunotherapy substantially clears plaque amyloid while increasing vessel-associated amyloid, but has been difficult to directly demonstrate.

Basic Science and Pathogenesis.

Background: The prevalence of Alzheimer's disease (AD) pathologies in people with Down syndrome (DS) is nearly 100%. In DS, overexpression of APP (on chr21) is associated with increased production of amyloid beta (Aβ) and the formation of phosphorylated tau (ptau) tangles. In the general population, women exhibit higher burdens of ptau compared to age-matched men with AD.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) related pathologies (i.e., neurofibrillary tangles [NFTs], amyloid-β plaques, and phosphorylated-TAR-DNA-binding-protein-43 [pTDP-43]) differ across sexes.

Basic Science and Pathogenesis.

Background: Several studies have found that oral and gut microbiome and their byproducts can impact Alzheimer's Disease (AD). The objective of our study is to analyze metagenomic sequencing data from paired oral and fecal microbiomes, along with clinical variables, to identify communities of bacteria associated with AD. This research aims to improve our understanding of the microbiome community matrix, and how these communities interact and correlate with AD status compared to healthy controls (HC) through an oral-gut microbial axis.