Network biology-based markers of extreme weather-induced neurodegeneration

Columbia University Health Sciences, New York NY

Investigators

Abstract

REVISED Project Summary – Project 2 In this project, we will strive to identify the biological mechanisms by which extreme weather events contribute to age-related neurodegeneration. We will leverage ongoing studies of Alzheimer’s disease in a New York City-based community cohort and employ laboratory models to explore biological mechanisms. Our approach will utilize multi-species and multiomic methods with network biology to pinpoint biological susceptibilities related to extreme weather. One of the most obvious dynamic and unpredictable external conditions is weather; age-associated pathologies are notably exacerbated by severe weather and temperature. Complementing Project 1, which uses national claims data to examine trends in age-related diseases such as Alzheimer’s disease (AD), this project will take a systems-level approach to delve into how extreme weather events alter biological pathways associated with age-associated neurodegeneration. We will use a combination of human prospective cohort data and well-controlled laboratory animal data to generate multiomic network models of extreme weather-induced biological disruption. In our cohort of human aging and neurodegeneration, we have used an exposome-based approach to generate data from plasma samples and from brain-derived circulating extracellular vesicles (EVs). We will examine how the New York City-specific Extreme Weather Index (EWI) influences network biology and disease-related outcomes. We will also use model organisms to examine the impact of a well-controlled example of extreme weather, namely, extreme temperatures, on biological networks. Our hypothesis is that EWI will disrupt specific biological nodes and that these disruptions will be reflected in neurodegeneration-associated outcomes. We will test this hypothesis through the following specific aims: Aim 1. To determine the effects of extreme weather events on Alzheimer’s disease-related changes in network biology. The residences of cohort participants are geocoded, allowing us to model complex extreme weather events with changes in network biology. Aim 2. To explore the use of brain-derived circulating EVs as a source of extreme weather-related biomarkers of neurodegeneration. Our team has access to data from brain-derived EVs from the same AD cohort as above. Aim 3. To determine the impact of dramatic temperature disruptions on network biology in model organisms. We will utilize the short-lifespan nematode worms ( C. elegans ) and Killifish ( N. furzeri ) to study the effects of extreme temperatures on age-associated pathology and lifespan using analogous measures to those used in Aims 1 and 2, allowing a cross-species analysis of temperature-induced changes in biological networks. Completion of these aims will provide a foundation for using multiomic-based network biology to study the impact of extreme weather events on human health and disease, contributing to the overall mission of CHART.