Emerging Concepts in Basic Science

This series highlighting basic dementia science will be a can’t-miss aspect of AAIC 2021.


In 2016, the AAIC Scientific Program Committee introduced the Emerging Concepts series, an innovative aspect of the Alzheimer’s Association International Conference program designed specifically for basic dementia science.

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Targeting Proteostasis in Neurodegeneration: Are We There Yet?

Chair: Ana Maria Cuervo, Albert Einstein College of Medicine — United States

Protein quality control is essential for maintenance of a healthy and functional proteome that can attend the multiplicity of cellular functions. Failure of the systems that contribute to protein homeostasis, the so called proteostasis networks, have been identified in the pathogenesis of multiple neurodegenerative disorders and demonstrated to contribute to disease onset and progression. Moreover, overall brain proteostasis decreases with age, further contributing to aggravate neuronal degeneration. The detailed molecular characterization of the components of the proteostasis network during the last decade has allowed development of multiple experimental models that have informed on the physiological relevance of proteostasis in the brain and have strengthened the connections between proteostasis failure and neurodegeneration. The better understanding of the principles governing neuronal and glial proteostasis has also given momentum to efforts attempting developing and testing of interventions targeting different proteostasis components in neurodegenerative diseases. In this session, we will provide an overview of the importance of neuronal proteostasis and the consequences of its failure in neurodegeneration (Morimoto) and discuss current efforts in targeting the three major components of the proteostasis network – chaperones (Gestwicki), proteasome (Bertolloti) and autophagy (Cuervo) for therapeutic purposes in the context of neurodegeneration.

Presentations:

Understanding Neurodegeneration at Single-Cell Resolution

Chair: Martin Kampmann, University of California, San Francisco — United States

To understand Alzheimer’s disease and other neurodegenerative diseases, we need to characterize disease processes in specific cell types in the brain. Recently developed single-cell approaches hold the promise to answer long-standing questions, such as mechanisms of selective vulnerability of specific neuronal subtypes, as well as specific states of glial cells that contribute to disease. This session will introduce several cutting-edge methodologies and their applications to brain disease.

Presentations:

Advances in Methodology for Structural Biology of Neurodegeneration

Chairs: Robert Tycko, National Institutes of Health (NIH) — United States and Judith Steen, Harvard University — United States

This Emerging Concepts session will focus on cutting-edge experimental techniques for characterizing molecular structures of protein assemblies that are associated with Alzheimer’s disease and related neurodegenerative diseases. Techniques to be discussed include cryogenic electron microscopy, solid state nuclear magnetic resonance, mass spectrometry based structural proteomics and quantitative modification mapping methods. Speakers will describe current capabilities, recent applications in protein structure determination in dementia science, prospects for future methodological advances, and synergies among complementary experimental approaches. Examples of applications that are enabled by new technology include investigations of amyloid polymorphism and its association with variations in disease characteristics, and studies of intramolecular and intermolecular interactions that drive protein aggregation. Furthermore, these studies lead us to functional and mechanistic studies that pave the way for therapeutics.

Presentations:


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