Imaging Alzheimer’s Disease with the ATN Framework and Beyond

Research suggests Alzheimer’s Disease (AD) is a complex, multifactorial condition difficult to distinguish in its early stage from other forms of dementia without the use of biomarker assessment. The NIA-AA ATN research framework focuses on the diagnosis of AD with biomarkers in living persons, which shifts the definition of AD in living people from a symptomatic to a biological construct. The ATN framework is a method to classify and characterize disease presence/state through evaluation of β amyloid deposition (A), pathologic tau (T), and neurodegeneration (N). Evidence of Aβ deposition is widely accepted as one of the preconditions for placement within the AD continuum while concurrent elevation of fibrillar tau confirms the pathologic indication of AD. Neurodegeneration measures, such as those derived from volumetric MRI and/or FDG-PET, serve to further elucidate critical staging information while also explaining significant variance within the A and T categories. However, as neuroscientific and disease models evolve, so too do the methods used to interrogate the pathophysiologic processes driving AD specific neurodegeneration. This allows an expansion beyond the ATN framework by integrating vascular, iron, and inflammation biomarkers to improve characterization of disease and likelihood of progression.

In this webinar, we will present the best practices of amyloid PET imaging and the most recent developments in the tau PET imaging space, including quantitative and visual assessment paradigms per the latest FDA approval. We will examine imaging of neurodegeneration and also explore emerging biomarkers beyond N. Techniques such as bi-compartment diffusion modeling, quantitative susceptibility mapping (QSM), arterial spin labeling (ASL), and breath-hold fMRI are capable of being deployed in a large-scale clinical trial setting and could aid patient selection and demonstrate therapeutic benefit. We will also highlight emerging PET markers for α-synuclein, microgliosis, and synaptic density, and their role in further refining AD staging.

The webinar will also explore how the multi-modal integration of molecular imaging, MRI, and fluid biomarkers can provide a robust ability to accurately parse patients along the AD cascade to provide optimal classification and treatment strategies as well as therapeutic efficacy.

Speakers

David Scott, Ph.D., Scientific Director, Bioclinica

Dr. David Scott’s aim is to facilitate drug development through standardized measurement of the neural correlates of neurodegenerative and other centrally mediated diseases. Since joining Bioclinica in 2012, Dr. Scott’s focus has been to enable MRI and molecular imaging solutions toward safety, eligibility and therapeutic efficacy endpoints. He works with Bioclinica’s staff radiologists, physicists, software engineers, and operational specialists on the design, execution, analysis and interpretation of imaging clinical trials in the neuroscience therapeutic area. His motivation is to effectively translate advanced neuroimaging tools from the lab to the clinic, so that therapeutic benefit can be delivered to patients around the world.

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Kate Adamczuk, Ph.D., Senior Scientist, Bioclinica

Dr. Kate Adamczuk oversees molecular imaging endpoints across phase I to III of multi-center neuroscience clinical trials. Her main goal is to utilize molecular imaging in combination with other biomarkers to facilitate the success of neuroscience clinical trials and accelerate patients’ benefits.

With more than ten years of experience in neuroscience and medical imaging, including positron emission tomography (PET), single-photon emission computerized tomography (SPECT), structural and functional magnetic resonance imaging (MRI), she develops clinical trial design strategies, serves as a scientific expert to Bioclinica clients and staff, plans and executes imaging research and designs and assists with the implementation of processing pipelines.

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Chris Conklin, Ph.D., MRI Scientist, Bioclinica

Dr. Chris Conklin works with experts in pharmaceutical and academic domains to translate these advanced imaging techniques into large, global multi-center trials. To support this endeavor, he designs, validates and standardizes the acquisition and quantitative analysis of advanced MRI biomarkers.

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