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Cell-Specific Proteome Dynamics and Biomolecule Imaging in Brain Aging and Alzheimer’s Disease: Bridging the Gap From Basic to Clinical Proteomics Workshop

Audience

Researchers interested in learning more about current progress and emerging technologies in studying single-cell proteomic changes and high-resolution imaging mass spectrometry (MS) in brain aging and age-related neurodegenerative diseases were invited to join this workshop.

Dates

Oct. 17, 2023 | 10 a.m.-5:30 p.m. ET

Oct. 18, 2023 | 10 a.m.-4:30 p.m. ET

Location

This hybrid workshop was available for participants to join virtually through Zoom.

Purpose and Background

Alzheimer’s disease is a complex, multifactorial condition typically lacking a single genetic cause. Understanding the molecular changes associated with Alzheimer’s and brain aging, spanning from genes to observable traits, requires a comprehensive grasp of protein components of brain cell types and their responses to environmental factors and insults.

This two-day meeting brought together NIA grantees and other leading researchers in the field of proteomics to discuss and explore recent advances, emerging technologies, and innovative approaches in the application of proteomics to the study of brain aging and neurodegenerative diseases, especially Alzheimer’s. The meeting featured lectures and panel discussions covering a wide range of topics, including (but not limited to):

  • The consequences of normal and pathological brain aging for regulating cell-specific dynamics of newly synthesized proteomes in, for example, synaptic plasticity
  • The roles of astrocytes and microglia in modulating proteome dynamics in synaptic degeneration and accumulation of Alzheimer’s-related pathologies
  • Impact of microenvironment, such as plaque accumulation, on the proteome dynamics in glia, microglia, and neuroinflammation
  • Establishing a small-molecule 3D brain atlas to understand the alteration, transportation, and distribution of small molecules
  • Developing computational and analytical tools to integrate MS imaging and single-cell omics measurements of brain tissue into “multiparameter” images with anatomical information
  • Optimizing high-throughput single-cell imaging MS and other imaging techniques for mapping and disease staging of normal and Alzheimer’s brains
  • Advances in MS-based shotgun proteomic approaches in fluid phase biomarker discovery and global proteomic analysis

Agenda

Note: The times listed below are all in Eastern Time.

Day 1 (Tuesday, Oct. 17)

10 a.m. Welcome remarks and overview of workshop objectives, NIA

Session 1

  • 10:20 a.m. Multimodal imaging mass spectrometry — connecting omics and imaging to discover molecular drivers of health and disease, Jeffrey Spraggins, Vanderbilt University
  • 10:50 a.m. Spatial dysregulation of lipidome and transcriptome in Alzheimer’s disease mouse models, Laura Beth McIntire, Weill Cornell Medicine
  • 11:20 a.m. Models of healthy human aging and spontaneous age-related pathology, Anita Disney, Duke University
  • 11:50 a.m. Blueprint for creating the functional brain spatial metabolome, lipidome, and glycome atlas in 3D, Ramon Sun, University of Florida

12:20 p.m. Lunch

Session 2

  • 12:50 p.m. Statistical methods and software for quantitative mass spectrometry and proteomics, Olga Vitek, Northeastern University
  • 1:20 p.m. Subcellular proteomics for aging: From single blastomeres (X. laevis) to single neurons (mouse), Peter Nemes, University of Maryland-College Park
  • 1:50 p.m. Multiscale mass spectrometry imaging for understanding neurochemical heterogeneity in Alzheimer’s disease, Fan Lam, University of Illinois
  • 2:20 p.m. Progress towards creating spatially resolved biomolecular atlas of the brain of Alzheimer’s disease via MALDI mass spectrometry imaging, Lingjun Li, University of Wisconsin-Madison

2:50 p.m. Break

Session 3

  • 3 p.m. New technologies for high throughput and deep plasma proteome analysis, Joshua Coon, University of Wisconsin-Madison
  • 3:30 p.m. Structural signature of blood proteins classifies the status of Alzheimer’s disease, John Yates, Scripps Research Institute
  • 4 p.m. Mass spectrometry as an agent of changing biological paradigms, Jennifer Van Eyk, Cedars-Sinai Medical Center
  • 4:30 p.m. Next generation translational proteomics of Alzheimer’s disease (TPAD2.0), Michael MacCoss, University of Washington
  • 5 p.m. Cell-type and cell signaling specific proteome analysis, Valina Dawson, Johns Hopkins University

5:30 p.m. Adjourn Day 1

Day 2 (Wednesday, Oct. 17)

10 a.m. Welcome to Day Two, NIA

Session 4

  • 10:10 a.m. Mapping cell-type specific proteomes to identify novel factors that promote cognitive resilience to Alzheimer’s disease, Catherine Kaczorowski, University of Michigan
  • 10:40 a.m. Harmonizing presynaptic proteostasis to prevent amyloid pathology in Alzheimer’s disease, Jeffrey Savas, Northwestern University
  • 11:10 a.m. Multi-layered proteomic analysis: Bridging human specimens and mouse models in Alzheimer’s disease research, Junmin Peng, St. Jude Children's Research Hospital
  • 11:40 a.m. Neuronal vulnerability in Alzheimer’s disease: Optimizing detection of spatial, proteomic, metabolomic, and cellular contributors, Merina Varghese, Icahn School of Medicine at Mount Sinai

12:10 p.m. Lunch

Session 5

  • 12:40 p.m. Determining how the subproteomes of astrocytes and neurons change in aging and Alzheimer’s disease, James Wohlschlegel, UCLA
  • 1:10 p.m. In vivo proximity biotinylation for native-state and cell type-specific proteomics of neurons and glia, Srikant Rangaraju, Yale University
  • 1:40 p.m. Quantifying tauopathies reveals novel mechanisms, Judith Steen, Harvard Medical School

2:10 p.m. Break

Session 6

  • 2:20 p.m. Proteomics of neuronal soma in Alzheimer’s disease, Harrison Specht, Parallel Squared Technology Institute, Northeastern University
  • 2:50 p.m. Cell type specific analysis of the nascent proteome, Hollis Cline, Scripps Research Institute
  • 3:20 p.m. Moderated discussion, Hollis Cline, John Yates, Jeffrey Spraggins

4:20 p.m. Closing remarks

4:30 p.m. Meeting adjourns

Contact Information

Please contact Dr. Austin Yang (austin.yang@nih.gov) with any questions about the workshop.

Additional Information

nia.nih.gov

An official website of the National Institutes of Health