Publications by authors named "Chelsea Alvarado"
Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe.
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- * Our research included looking at both common and rare gene variants connected to the NLRP3 inflammasome, as well as assessing the potential effects of related cytokines (IL-1β and IL-18) on PD.
- * The results showed no significant link between NLRP3 variations and PD, suggesting that the NLRP3 inflammasome may not be a viable target for treatment or play a role in the disease's development.
Article Synopsis
- Recent FDA approvals for Alzheimer treatments like lecanemab and aducanumab emphasize the need for understanding biological mechanisms to develop effective therapies for neurodegenerative disorders.
- The study utilizes genetic data to identify 116 genes associated with Alzheimer and other neurodegenerative diseases, classifying them based on their potential for drug development.
- A new web platform is introduced to help researchers easily explore therapeutic targets, encouraging further investigation and collaboration in tackling these challenging diseases.
Background: Single-cell RNA sequencing has opened a window into clarifying the complex underpinnings of disease, particularly in quantifying the relevance of tissue- and cell-type-specific gene expression.
Methods: To identify the cell types and genes important to therapeutic target development across the neurodegenerative disease spectrum, we leveraged genome-wide association studies, recent single-cell sequencing data, and bulk expression studies in a diverse series of brain region tissues.
Results: We were able to identify significant immune-related cell types in the brain across three major neurodegenerative diseases: Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease.
Activation of the NLRP3-inflammasome has been implicated in Parkinson's disease based on and studies. Clinical trials targeting the NLRP3-inflammasome in Parkinson's disease are ongoing. However, the evidence supporting NLRP3's involvement in Parkinson's disease from human genetics data is limited.
View Article and Find Full Text PDFIdentification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study.
Lancet Neurol
November 2023
Background: An understanding of the genetic mechanisms underlying diseases in ancestrally diverse populations is an important step towards development of targeted treatments. Research in African and African admixed populations can enable mapping of complex traits, because of their genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. We aimed to do a comprehensive genome-wide assessment in African and African admixed individuals to better understand the genetic architecture of Parkinson's disease in these underserved populations.
View Article and Find Full Text PDFSingle cell RNA sequencing has opened a window into clarifying the complex underpinnings of disease, particularly in quantifying the relevance of tissue- and cell-type-specific gene expression. To identify the cell types and genes important to therapeutic target development across the neurodegenerative disease spectrum, we leveraged genome-wide association studies, recent single cell sequencing data, and bulk expression studies in a diverse series of brain region tissues. We were able to identify significant immune-related cell types in the brain across three major neurodegenerative diseases: Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Parkinson's Diseases.
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- The study focuses on understanding genetic factors contributing to Parkinson's disease (PD) within African and African admixed populations to advance precision medicine.
- A genome-wide assessment involving nearly 200,000 individuals identified a significant risk factor linked to the gene at locus rs3115534-G, with a strong correlation to PD onset and a mechanism related to gene expression rather than coding mutations.
- The findings suggest this genetic variant is uniquely prevalent among African ancestries, highlighting the importance of diverse populations in researching complex diseases like PD.
Article Synopsis
- Scientists studied Parkinson's disease to look for rare genetic differences that might help explain the illness.
- They used data from thousands of people with Parkinson's disease and healthy people to find important genes linked to the disease.
- They discovered some genes, like GBA1 and LRRK2, that are already known to be related to Parkinson's, but they also found new genes that might help us understand how the disease works, especially in terms of inflammation in the brain.
Article Synopsis
- GWAS of Alzheimer's disease have mostly focused on individuals of European descent, overlooking genetic differences in other global populations.
- This research conducted a large multi-ancestry GWAS meta-analysis, identifying two new disease-related genetic loci on chromosome 3 and refining nine loci linked to Alzheimer’s risk.
- The study underscores the significance of including diverse ancestries in genetic research to better understand risk factors for Alzheimer's disease and related dementias.
Article Synopsis
- Neurodegenerative diseases (NDDs) often share similar symptoms and genetic risk factors, indicating a possible interconnectedness among them.
- This study clusters patients with five major NDDs using genetic data, revealing significant overlaps in genetic causes and supporting the idea of neurodegeneration as a spectrum.
- The findings suggest that some patients lack common genetic risk factors, hinting at other influences like environmental factors, and emphasize the need for further research to understand how these variants affect disease development and treatment.
Article Synopsis
- Recent FDA approvals like Lecanemab and Aducanumab for Alzheimer's Disease stress the need for better treatments for neurodegenerative disorders, especially as the global population ages.
- This study presents a comprehensive framework to identify therapeutic targets using genetic data and provides insights into the mechanisms of disease, identifying numerous target genes for various conditions including Alzheimer's and Parkinson's disease.
- A user-friendly web platform is also created to allow researchers and the community to easily explore these therapeutic targets, facilitating future drug discovery and development.
Neurodegeneration with brain iron accumulation (NBIA) represents a group of neurodegenerative disorders characterized by abnormal iron accumulation in the brain. In Parkinson's Disease (PD), iron accumulation is a cardinal feature of degenerating regions in the brain and seems to be a key player in mechanisms that precipitate cell death. The aim of this study was to explore the genetic and genomic connection between NBIA and PD.
View Article and Find Full Text PDFThe neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly . Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets.
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