Biomarkers Of Neuroinflammation PDF Download

Despite decades of research, Alzheimer's disease (AD) remains poorly understood and without effective treatment or prevention. The presence of amyloid beta and tau pathology together is thought to result in neurodegeneration, or the loss of synapses and neurons, but the mechanism by which the two interact to produce this neurodegeneration is unknown. Recent data suggest an interplay between inflammation and iron dysregulation in the pathogenesis of AD that may be a key component of AD pathology. Most of this work, however, has lacked the simultaneous analysis of iron, inflammation, and hallmark AD pathology, necessary to elucidate the mechanistic link between iron and neurodegeneration in AD. To address this gap and deliver iron as a biomarker for AD, we have developed a novel, multimodal ex vivo imaging pipeline, integrating novel correlative MR-histology tools with advanced microscopy, including electron microscopy and x-ray microscopy techniques, to interrogate iron deposition and oxidation state in human brain tissue in situ. We have additionally implemented a novel prospective motion correction system for high-field MRI to enable ultra-high-resolution human brain imaging and facilitate the translation of our ex vivo findings to the patient setting. While the initial application of these tools has been to validate iron as a biomarker of neuroinflammation in AD, we have developed a broadly applicable set of imaging tools with the potential to molecularly validate and translate MRI-based biomarkers across tissue types and diseases.