Browsing by Author "Anderson, Matthew"

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    Considerations for widespread implementation of blood-based biomarkers of Alzheimer's disease
    (Wiley, 2024) Mielke, Michelle M.; Anderson, Matthew; Ashford, J. Wesson; Jeromin, Andreas; Lin, Pei-Jung; Rosen, Allyson; Tyrone, Jamie; VandeVrede, Lawren; Willis, Deanna; Hansson, Oskar; Khachaturian, Ara S.; Schindler, Suzanne E.; Weiss, Joan; Batrla, Richard; Bozeat, Sasha; Dwyer, John R.; Holzapfel, Drew; Jones, Daryl Rhys; Murray, James F.; Partrick, Katherine A.; Scholler, Emily; Vradenburg, George; Young, Dylan; Braunstein, Joel B.; Burnham, Samantha C.; de Oliveira, Fabricio Ferreira; Hu, Yan Helen; Mattke, Soeren; Merali, Zul; Monane, Mark; Sabbagh, Marwan Noel; Shobin, Eli; Weiner, Michael W.; Udeh-Momoh , Chinedu T.; Medicine, School of Medicine
    Diagnosing Alzheimer's disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood-based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and the ethical management of test results, must be addressed for widespread clinical implementation of BBMs in the United States. The Global CEO Initiative on Alzheimer's Disease BBM Workgroup convened to address these challenges and provide recommendations that underscore the importance of evidence-based guidelines, improved training for health-care professionals, patient empowerment through informed decision making, and the necessity of community-based studies to understand BBM performance in real-world populations. Multi-stakeholder engagement is essential to implement these recommendations and ensure credible guidance and education are accessible to all stakeholders.
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    Hedgehog Signaling Regulates Apical Actin Morphology
    (Office of the Vice Chancellor for Research, 2016-04-08) Anderson, Matthew; Hege, Melissa; Berbari, Nicolas; Perrin, Benjamin
    Stereocilia are highly patterned actin based cell protrusions found on the apical surface of auditory hair cells. They are formed mainly from bundled filamentous actin and its associated actin cross-linking proteins. Interestingly, stereocilia develop around another cell appendage, the microtubule based kinocilium, which is the primary cilium for a hair cell. Primary cilia are found on most somatic cells and play a significant role in the regulation and proper transduction of the Hedgehog (Hh) pathway. In the current study, we are testing the hypothesis that Hh pathway activity can alter actin bundling and elongation. In support of this idea, ectopic activation or repression of Hh signaling changed the morphology of stereocilia in vivo. To further test our hypothesis, we used a CL4 porcine kidney epithelial cell culture system stably expressing the actin crosslinking protein ESPN fused to green fluorescent protein. These cells serve as an in vitro model of apical actin protrusions similar to mature stereocilia in vivo. We manipulated Hh signaling in these cells using both a genetic and a pharmacological approach. In the pharmacological approach, CL4 cells were treated with the hedgehog agonist (Purmophamine) and antagonist (Cyclopamine), at varying concentrations for 48 hours. Genetically, the Hh pathway was ectopically activated by overexpressing the transcription factor Gli1, Gli2, Gli3, and SmoA1 repressed by expressing Gli3R. Immunofluorescent (IF) and scanning electron microscopy (SEM) revealed that CL4 cells dramatically altered the apical actin structures under these conditions. In particular, activating Gli transcription decreased apical actin-based structures while antagonizing activity resulted in more actinbased protrusions. This data strongly supports the hypothesis that the Hh signaling pathway can regulate the actin cytoskeleton.
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    Recommendations for clinical implementation of blood-based biomarkers for Alzheimer's disease
    (Wiley, 2024) Mielke, Michelle M.; Anderson, Matthew; Ashford, J. Wesson; Jeromin, Andreas; Lin, Pei-Jung; Rosen, Allyson; Tyrone, Jamie; Vandevrede, Lawren; Willis, Deanna R.; Hansson, Oskar; Khachaturian, Ara S.; Schindler, Suzanne E.; Weiss, Joan; Batrla, Richard; Bozeat, Sasha; Dwyer, John R.; Holzapfel, Drew; Jones, Daryl Rhys; Murray, James F.; Partrick, Katherine A.; Scholler, Emily; Vradenburg, George; Young, Dylan; Braunstein, Joel B.; Burnham, Samantha C.; de Oliveira, Fabricio Ferreira; Hu, Yan Helen; Mattke, Soeren; Merali, Zul; Monane, Mark; Sabbagh, Marwan Noel; Shobin, Eli; Weiner, Michael; Udeh-Momoh, Chinedu T.; Medicine, School of Medicine
    Blood-based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to provide recommendations for two clinical implementational pathways for BBMs: one for current use for triaging and another for future use to confirm amyloid pathology. These pathways provide a standardized diagnostic approach with guidance on interpreting BBM test results. Integrating BBMs into clinical practice will simplify the diagnostic process and facilitate timely access to DMTs for eligible patients.