Alzheimer's Disease Research Center

OVERALL PROJECT SUMMARY In this application to renew Columbia University’s Alzheimer’s Disease Research Center (ADRC), we propose to continue our Center’s tradition that has existed at Columbia since 1989, originally as a P50 that then transitioned to a P30 in 2020. Building off our prior accomplishments and guided by the current Funding Opportunity Announcement (FOA), the general overarching objective is to continue to foster highly interactive, cutting-edge research on Alzheimer’s disease (AD) and related dementias, both locally in our extensive campus and more globally with other institutions and national consortia. As also articulated in the FOA, Centers are encouraged to leverage their home institution’s distinct strengths and expertise to pursue thematic goals. Through internal discussions and with our External Advisory Committee, we will maintain, but also expand, our current thematic focus, which is to better understand how AD’s pathogenic biological pathways (i.e., the ‘immune response’ and the ‘endosomal trafficking’ pathways) interact with AD’s cardinal pathologies, (i.e., amyloid pathology, tau pathology, and neurodegeneration). Given recent advancements and some of our Center’s distinct strengths, we propose to expand the theme by triangulating the pathways-pathologies relationship with two other interrelated topics. As discussed in more detail throughout this proposal, one is ‘clinical trials’ which, inspired by the recent therapeutic breakthroughs, are anticipated to proliferate. The other is ‘diversity’ (e.g., underrepresented racial, ethnic, or socioeconomic groups) as it relates to the impact of pathogenic mechanisms and to clinical trials. Questions that exemplify this theme include: Is efficacy and/or toxicity in trials influenced by the pathways-pathologies relationship or on diversity? Does the pathways-pathologies relationship vary across underrepresented groups, which might inform clinical trial design? Why have clinical trials suffered from lack of social diversity? Might deeper insight into the pathways-pathologies relationship lead to novel precision-medicine biomarkers, therapeutic targets, and drug discovery? We propose to achieve our general and thematic goals through our well-integrated Cores, which collectively establishes an infrastructure that generates a rich array of resources, biospecimens, and expertise. Besides our Director, Dr. Scott Small, and our Co-Directors, Drs. Adam Brickman, Jennifer Manly, and James Noble, these cores include a Clinical Core led by Dr. James Noble, a ‘Data Management and Statistical’ Core led by Dr. Howard Andrews, a Neuropathology Core led by Dr. Andrew Teich, a Biomarker Core led by Dr. Adam Brickman, a an ‘Outreach, Retention, an Engagement’ Core led by Dr. Miguel Arce, a Genetics Core led by Dr. Christiane Reitz, a Neuroimmunology Core led by Dr. Phillip De Jager, and a ‘Research Education’ Module led by Dr. Stephanie Cosentino.