Project Abstract: Alzheimer's disease and related dementias (ADRD) affect tens of millions of people around the world and represent a staggering challenge for patients, families, and healthcare systems. For some who present with mild levels of cognitive impairment, there is rapid worsening of cognition and function, whereas for others, the rate of progression can be absent or much slower. Understanding this variability in rate of progression is critically important to patients, families, and clinical researchers alike, and is not well-predicted by common, clinically available biomarker tools. Blood-based markers of AD pathology and neurodegeneration have potential for widespread use in clinical research and even clinical care, due to their non-invasiveness, cost relative to neuroimaging, and lack of medical contraindications to limit their use. Here we examine a set of newly developed, blood-based AD biomarkers (including neurofilament light chain, phospho-tau species, tau, and Ab fragments) that may fill this gap. Leveraging prospectively acquired samples from a large clinic population and from local clinical research studies, we will determine how these plasma measures relate to variable rates of "real-world" cognitive and functional decline, as well as to imaging-based measures of neurodegeneration and AD pathologic progression.