10 research outputs found
A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease
Phenotypes of eosinophilic esophagitis (EoE) are not well characterized
Su1141 ICD-9 Codes Do Not Reliably Identify Cases of Eosinophilic Esophagitis: A Cautionary Tale
Su1142 Can an Internet Search Engine Provide Clues Into the Evolving Epidemiology of Eosinophilic Esophagitis?
Su1847 Decreasing Frequency of the Fibrostenotic Phenotype of Eosinophilic Esophagitis: Time Trends Over the Past Decade
Su1848 Differences in Presentation of Eosinophilic Esophagitis by Atopic Status, Eosinophilia, and Age of Symptom Onset: An Analysis of Non-Endoscopic Phenotypes
Su1833 Eosinophilic Esophagitis Is a Progressive Fibrostenotic Disease: Insights From a Phenotypic Analysis
CHRNA5 links chandelier cells to severity of amyloid pathology in aging and Alzheimer’s disease
Abstract Changes in high-affinity nicotinic acetylcholine receptors are intricately connected to neuropathology in Alzheimer’s Disease (AD). Protective and cognitive-enhancing roles for the nicotinic α5 subunit have been identified, but this gene has not been closely examined in the context of human aging and dementia. Therefore, we investigate the nicotinic α5 gene CHRNA5 and the impact of relevant single nucleotide polymorphisms (SNPs) in prefrontal cortex from 922 individuals with matched genotypic and post-mortem RNA sequencing in the Religious Orders Study and Memory and Aging Project (ROS/MAP). We find that a genotype robustly linked to increased expression of CHRNA5 (rs1979905A2) predicts significantly reduced cortical β-amyloid load. Intriguingly, co-expression analysis suggests CHRNA5 has a distinct cellular expression profile compared to other nicotinic receptor genes. Consistent with this prediction, single nucleus RNA sequencing from 22 individuals reveals CHRNA5 expression is disproportionately elevated in chandelier neurons, a distinct subtype of inhibitory neuron known for its role in excitatory/inhibitory (E/I) balance. We show that chandelier neurons are enriched in amyloid-binding proteins compared to basket cells, the other major subtype of PVALB-positive interneurons. Consistent with the hypothesis that nicotinic receptors in chandelier cells normally protect against β-amyloid, cell-type proportion analysis from 549 individuals reveals these neurons show amyloid-associated vulnerability only in individuals with impaired function/trafficking of nicotinic α5-containing receptors due to homozygosity of the missense CHRNA5 SNP (rs16969968A2). Taken together, these findings suggest that CHRNA5 and its nicotinic α5 subunit exert a neuroprotective role in aging and Alzheimer’s disease centered on chandelier interneurons
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Joint Submission of Antitrust Economists, Legal Scholars, and Practitioners to the House Judiciary Committee on the State of Antitrust Law and Implications for Protecting Competition in Digital Markets
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Joint Submission of Antitrust Economists, Legal Scholars, and Practitioners to the House Judiciary Committee on the State of Antitrust Law and Implications for Protecting Competition in Digital Markets
A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease
Phenotypes of eosinophilic esophagitis (EoE) are not well characterized