Evaluating Cerebrospinal Fluid Biomarkers in Alzheimer's, Progressive Supranuclear Palsy Subjects, and Controls

This is an experimental medicine study to evaluate the kinetics of cerebrospinal fluid (CSF) biomarkers in subjects with Alzheimer's disease (AD) or progressive supranuclear palsy (PSP) compared to healthy controls using a heavy water (2H2O) labeling method. This study is exploring the time profile of appearance and disappearance of pulse deuterium-labeled cargo proteins in CSF of subjects with AD and/or PSP, which is different from healthy controls, due to deficits in fast axonal transport.

Primary Objective: To compare the time profile of appearance and disappearance in CSF of pulse deuterium-labeled chromogranin B, sAPPα and β-Trace in AD and PSP subjects compared to healthy controls. Secondary Objectives: * To measure body water enrichment of deuterium in saliva and plasma (2H-enrichment (%)) * To explore the effect of age on the kinetics of deuterium labeling of CSF biomarkers * To assess intra and inter subject variability of deuterium-labeling of chromogranin B, sAPPα and β-Trace Subjects will undergo screening evaluations to determine eligibility prior to heavy water (2H20) administration. Eligible subjects will be admitted to the clinical facility on Day -1. On Day 1, subjects will ingest small doses of 2H20 during their inpatient stay. They will also drink 2H20 for 7 more days. Subjects will undergo two lumbar punctures (LPs) for CSF samples. Subjects will return to the study site approximately 7 days after the last LP (or early termination) for a follow-up assessment and discharge.