Over the past 7 years, our team succeeded in developing an assay to measure brain HDL using the Ion Mobility Technique. This method was originally developed for blood lipoproteins by our long-term collaborator Ronald Krauss at UCSF. Congratulations to Ashley Martinez (who led the biochemistry studies to isolate HDL from cerebrospinal fluid), Gali Weissberger (who analyzed the cognitive performance measures), Susan Kuklenyik (who performed the mass spectrometry analysis of lipids and proteins), and the many members of the team. When we started in 2015, we did not imagine how long this process will take. But here we are. The original discovery of HDL particles in blood in 1929 led to several advances in drug discovery for cardiovascular disease treatment and prevention. In this work and for the first time, we measure HDL particles in cerebrospinal fluid as a surrogate of brain HDL and find that greater levels of small HDL correlate with better performance on cognitive measures and less accumulation of brain amyloid. Now that we have this new biomarker, our next step is to figure out what promotes the formation of these small HDL particles in the brain. Such new discoveries could then lead to a new list of medications in our fight against Alzheimer’s. Our work is featured in Alzheimer’s and Dementia journal.