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: 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: Brain deposits of amyloid-β (Aβ), one of the hallmark pathologies of Alzheimer disease (AD), are consistently present in people with Down syndrome (DS) after the age of 30 years. Positron emission tomography (PET) radioligands like [3H]Pittsburgh Compound-B (PiB) allow for visualizing Aβ accumulation in living people. In DS, the earliest and strongest PiB-PET retention is in the striatum, differing from late-onset AD.

Transplantation of gasdermin pores by extracellular vesicles propagates pyroptosis to bystander cells.

Pyroptosis mediated by gasdermins (GSDMs) plays crucial roles in infection and inflammation. Pyroptosis triggers the release of inflammatory molecules, including damage-associated molecular patterns (DAMPs). However, the consequences of pyroptosis-especially beyond interleukin (IL)-1 cytokines and DAMPs-that govern inflammation are poorly defined.

A review of clopidogrel resistance in lower extremity arterial disease.

Objective: Lower extremity arterial disease (LEAD) is a prevalent condition that produces a significant burden on health care systems. Patients with LEAD have an increased risk of major adverse cardiovascular events as well as major adverse limb events. Despite significant variation in guidance on antiplatelet therapy for LEAD worldwide, many governing bodies recommend clopidogrel as the preferred single anti-platelet agent.