Since its inception in 1990, the Alzheimer's Disease Research Center (ADRC) at New York University Langone Health has facilitated pioneering research to define transitions from normal aging to the subjective cognitive decline (SCD), mild cognitive impairment (MCI), and early dementia stages of AD; as well as AD biomarker development. Here we propose to continue this long-standing successful research direction with a focus on understanding disease heterogeneity and delineating biomarkers and their role in these transitions, with the long-term goal of helping to develop novel interventions that will delay or prevent cognitive decline. The NYU ADRC has built an infrastructure that supports innovative research on AD and related dementias (ADRD) to help achieve the NAPA goal of a cure by 2025. This will be facilitated by our nine highly successful and interactive Cores (Admin; Clinical; Data Management & Statistical [DMS]; Neuropathology; Outreach, Education & Engagement [ORE]; Neuroimaging; Biomarker; Psychosocial; and Research Education Component [REC]). Together, our highly integrated cores will achieve the following aims: Aim 1. Enhance the performance of innovative research in ADRC by maintaining nine cores that focus on delineating biomarkers of the transitions from normal aging to SCD, MCI, and early dementia, and determining their roles to help develop novel interventions that delay or prevent these transitions. We will also facilitate training in this area. Aim 2. Contribute to the national network of ADRCs by providing clinical data, autopsy diagnoses, neuroimaging and biosamples to NACC and NCRAD, as well as to other research community collaborative efforts in ADRD. Aim 3. Recruit and retain a diverse subject population from clinical and community settings, via the ORE and Psychosocial Cores, with concomitant engagement of the local scientific and lay community in ADRD with seminars, poster sessions and the developmental projects via the Admin, ORE, and REC Cores. Aim 4. Foster the development of novel avenues of investigation with methodological developments by the cores (via innovative cognitive assessments, neuroimaging techniques, biomarkers and proteomic approaches), and encourage, recruit, and select developmental projects. Aim 5. Accelerate translational research across the ADRD spectrum by using biomarkers to better define the underlying disease heterogeneity and foster the development of novel therapeutic interventions that consider this heterogeneity. Aim 6. Facilitate the education and training of a diverse ADRD workforce. Our Center will enhance the scientific community's understanding of ADRD and expand the next generation of diverse ADRD scientists, via combined efforts of the Admin, ORE, and REC Cores. In summary, the NYU ADRD has facilitated pioneering research that defined the stage transitions from normal aging to dementia, and contributed to AD biomarker development from its inception. In the next five years of funding, this focus will be expanded by: 1) improving our understanding of disease heterogeneity; 2) identifying new biomarkers that will allow early detection; and 3) fostering research that will develop effective therapeutic interventions.