Abstract The overall goal of this project is to address the critical unmet need for longitudinal data from clinical outcome assessments (COAs) and plasma biomarkers for the rare syndrome of posterior cortical atrophy (PCA) to enable clinical trial readiness with currently available candidate therapeutics. PCA was described in 1988 in five patients with progressive dementia that began with higher-order visual dysfunction and relative sparing of `memory, insight, and judgment' with a predominance of atrophy in the parieto-occipital regions. We now understand that Alzheimer's disease (AD) is the underlying pathology in up to 100% of patients and onset usually occurs at a younger age, between age 50 and 64 years. The visual-predominant phenotype and lack of longitudinal data combine to impede clinical trial design for PCA. Notably, widely used COAs for AD clinical trials rely on changes in memory and domains that are relatively spared in PCA, and assessments of higher-order visual impairment are very limited in COAs in AD trials. For these reasons, PCA presentations of AD do not meet the inclusion criteria for traditional AD clinical trials. To overcome barriers to inclusion and to clinical trial design, we will enroll 25 people with PCA, defined by 2017 diagnostic criteria, and longitudinally assess, over one year the following outcomes 1) one patient-reported and one informant-reported PCA-specific COA, 2) a novel PCA COA staging method using a probabilistic ordering of decline on 13 tasks that are inclusive of higher-order visual functions, 3) AD-COAs widely used in AD clinical trials, and 4) plasma biomarkers of neurodegeneration and AD pathology. In Aims 1 and 2, we will measure the responsiveness of COAs to PCA progression and the reliability and internal consistency of an informant-based PCA-specific COA. The convergent validity and responsiveness of the novel PCA staging COA will be assessed in Aim 2. Lastly, we will evaluate the responsiveness of plasma biomarkers to clinical changes in exploratory Aim 3 in anticipation of the future use of biomarkers as surrogate markers of treatment impact in a clinical trial. The establishment of these longitudinal benchmark measures using COAs and plasma biomarkers will serve as an essential foundation for enabling PCA clinical trial readiness with promising and currently available candidate therapeutics.