Slavery in Rhode Island: Awakening a Forgotten Past (poster)

This map serves to raise awareness about the history of slavery in Rhode Island. Despite having played an active role in the Trans-Atlantic slave trade, Rhode Island’s involvement is often overlooked or omitted from what we are traditionally taught in historically influenced classes at Providence College. Instead of integrating local history and knowledge into our own curriculum, we learn about slavery through a Eurocentric, Westernized lens. We aim to challenge our narrow teachings about slavery and widen our perspectives by constructing alternative narratives that go against the metanarrative. This map displaces the untold narratives of four areas in Rhode Island: Providence, Bristol, Narragansett and Newport. Through these stories, we seek to highlight and draw attention to the set of skills, the culture, and the sense of humanity that Black individuals retained throughout their enslavement. By presenting Rhode Island’s involvement in the slave trade, we aim to remind our community that slavery not only existed thousands of miles away from us but also occurred in many familiar places we visit every day. We would not only like to shed light on the hidden history of slavery, but to also raise consciousness about how this history should play a vital part in our education at Providence College

The Clinical Promise of Biomarkers of Synapse Damage or Loss in Alzheimer’s Disease

BACKGROUND: Synapse damage and loss are fundamental to the pathophysiology of Alzheimer's disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss. The key points of this review include the following: Synapse loss is a downstream effect of amyloidosis, tauopathy, inflammation, and other mechanisms occurring in AD.Synapse loss correlates most strongly with cognitive decline in AD because synaptic function underlies cognitive performance.Compounds that halt or reduce synapse damage or loss have a strong rationale as treatments of AD.Biomarkers that measure synapse degeneration or loss in patients will facilitate clinical development of such drugs.The ability of methods to sensitively measure synapse density in the brain of a living patient through synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, concentrations of synaptic proteins (e.g., neurogranin or synaptotagmin) in the cerebrospinal fluid (CSF), or functional imaging techniques such as quantitative electroencephalography (qEEG) provides a compelling case to use these types of measurements as biomarkers that quantify synapse damage or loss in clinical trials in AD. CONCLUSION: A number of emerging biomarkers are able to measure synapse injury and loss in the brain and may correlate with cognitive function in AD. These biomarkers hold promise both for use in diagnostics and in the measurement of therapeutic successes

Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer’s disease

Data from Colom-Cadena et al Published in Acta Neuropathologica in 2024. Abstract: Synapse loss correlates with cognitive decline in Alzheimer’s disease, and soluble oligomeric amyloid beta (Aβ) is implicated in synaptic dysfunction and loss. An important knowledge gap is the lack of understanding of how Aβ leads to synapse degeneration. In particular, there has been difficulty in determining whether there is a synaptic receptor that binds Aβ and mediates toxicity. While many candidates have been observed in model systems, their relevance to human AD brain remains unknown. This is in part due to methodological limitations preventing visualization of Aβ binding at individual synapses. To overcome this limitation, we combined two high resolution microscopy techniques: array tomography and Förster resonance energy transfer (FRET) to image over 1 million individual synaptic terminals in temporal cortex from AD (n=11) and control cases (n=9). Within presynapses and postsynaptic densities, oligomeric Aβ generates a FRET signal with transmembrane protein 97. Further, amyloid beta generates a FRET signal with cellular prion protein, and postsynaptic density 95 within postsynapses. Transmembrane protein 97 is also present in a higher proportion of postsynapses in Alzheimer’s brain compared to controls. We inhibited Aβ / transmembrane protein 97 interaction in a mouse model of amyloidopathy by treating with the allosteric modulator CT1812. CT1812 drug concentration correlated negatively with synaptic FRET signal between transmembrane protein 97 and Aβ. In human induced pluripotent stem cell derived neurons, transmembrane protein 97 is present in synapses and colocalizes with Aβ when neurons are challenged with human Alzheimer’s brain homogenate. Transcriptional changes are induced by Aβ including changes in genes involved in neurodegeneration and neuroinflammation. CT1812 treatment of these neurons caused changes in gene sets involved in synaptic function. These data support a role for transmembrane protein 97 in the synaptic binding of Aβ in human Alzheimer’s disease brain where it may mediate synaptotoxicity

Crowdsourcing digital health measures to predict Parkinson’s disease severity: the Parkinson’s Disease Digital Biomarker DREAM Challenge

Consumer wearables and sensors are a rich source of data about patients' daily disease and symptom burden, particularly in the case of movement disorders like Parkinson's disease (PD). However, interpreting these complex data into so-called digital biomarkers requires complicated analytical approaches, and validating these biomarkers requires sufficient data and unbiased evaluation methods. Here we describe the use of crowdsourcing to specifically evaluate and benchmark features derived from accelerometer and gyroscope data in two different datasets to predict the presence of PD and severity of three PD symptoms: tremor, dyskinesia, and bradykinesia. Forty teams from around the world submitted features, and achieved drastically improved predictive performance for PD status (best AUROC = 0.87), as well as tremor- (best AUPR = 0.75), dyskinesia- (best AUPR = 0.48) and bradykinesia-severity (best AUPR = 0.95)