Risultati per: Studio chiarisce come l’Alzheimer si diffonde nel cervello

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Abstract 13370: Single-Cell RNA-seq Reveals Transcriptomic Modulation of Alzheimer’s Disease by Activated Protein C

Circulation

Circulation, Volume 148, Issue Suppl_1, Page A13370-A13370, November 6, 2023. Introduction:Alzheimer’s Disease (AD) causes neuroinflammation characterized by degradation of neurological functions resulting in memory loss and confusion. Activated Protein C (APC), a plasma zymogen, has shown promising cytoprotection, anti-inflammation, and anti-apoptotic properties. ScRNA-seq allows for examining the underlying mechanisms by which APC therapy on AD at the cellular level.Hypothesis:APC treatment can ameliorate AD symptoms of 5xFAD transgenic mice. The scRNA Seq analysis could provide detailed responses of various cell populations to Alzheimer’s disease pathogenesis and molecular aspects of APC therapy.Methods:Whole brain tissue were collected at 7 months, APC-treated 5xFAD mice received daily recombinant APC or saline injections. The 10x Genomics Next Gem kit was used to dissociate the tissue for sequencing. Bioinformatic analysis was performed using Seurat in R and an integrated dataset was used to compare multiple single-cell samples.Results:Bioinformatic analysis of 5xFAD versus wild type (WT) C57BL/6J mouse brain revealed much of the sample consists of microglial cells. Interestingly, 5xFAD versus WT brains have notable decreases in astrocyte and neuron populations. Administration of recombinant APC rebounds these populations to comparable levels as WT while dramatically reduces the microglial population in 5xFAD versus WT brain. The largest proportion of oligodendrocytes are also recorded after APC treatment. Differential expression testing conveys transcriptomic regulation of known AD critical genes such asApoe,Ctsb,Trem2, andTyrobpby APC. Consequently, GO term enrichment uncovers inflammatory biological processes such as microglial activation to be downregulated by APC-treated 5xFAD. Additionally, recuperation of nervous system developmental processes was found in APC-treated 5xFAD mice.Conclusions:APC treatment drastically impacts the cellular pathophysiology of AD. Differential expression testing of APC treated 5xFAD versus WT mice revealed transcriptomic downregulation of AD implicated genes throughout multiple cell-types. Administration of APC significantly impacts AD implicated genes associated with AD pathogenesis through enrichment analysis.

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Novembre 2023

Abstract 14800: Alzheimer’s Disease and Related Dementias (ADRD) Limits Days at Home Among Medicare Beneficiaries Hospitalized for Heart Failure (HF)

Circulation

Circulation, Volume 148, Issue Suppl_1, Page A14800-A14800, November 6, 2023. Background:Alzheimer’s disease and related dementias (ADRD) are highly prevalent among adults with heart failure (HF). HF is associated with disability among older adults, especially those with ADRD. This may impact aging in place after HF hospitalizations, which is concerning given this is an important outcome for patients recovering from serious illnesses. We aimed to examine the association between ADRD and aging in place among Medicare beneficiaries hospitalized for HF.Methods:We identified 80,694 fee-for-service beneficiaries hospitalized for HF between 2017 and 2019 in a 20% random sample of Medicare claims. HF hospitalization and ADRD were identified using ICD codes. The primary outcome was restricted home time, a patient-centered claims-based measure of successful aging in place defined as spending ≥ 10 days not at home (e.g., hospitalized, nursing home, inpatient facility) over 6 months post-discharge. Multivariable logistic regression was used to examine the association between ADRD and restricted home time adjusting for demographic and clinical characteristics; secondary analyses evaluated the likelihood of returning to pre-hospitalization days at home 6 months post-discharge.Results:Eighteen percent (n= 14,503/80,694) of adults hospitalized for HF had concurrent ADRD. HF patients with ADRD were older (83 vs 77 years), more likely to be female (56% vs 48%), and have dual Medicaid/Medicare eligibility (27% vs 21%), but had similar hospital length of stays and days at home preceding HF hospitalization compared to those without ADRD. Of HF patients with ADRD, 63% had restricted home time (vs. 51% without ADRD) and 52% failed to return to baseline days at home (vs. 42% without ADRD). In adjusted models, older adults with ADRD had 34% greater odds of experiencing restricted home time (OR=1.34, 1.30-1.40), and 20% lower odds of returning to baseline days at home (OR=0.80, 0.77-0.83) 6 months post- discharge than those without ADRD.Conclusions:HF hospitalizations impact the ability of older adults to successfully age in place, especially among those with ADRD. Tailored post-discharge care solutions are urgently needed to address the challenges faced by HF patients with ADRD.

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Novembre 2023
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