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

Inclusion Criteria: All subjects * Body Mass Index of 18-32. * Subjects can have common non-neurological age-related disorders (hypertension, diabetes) and on stable medication for the last 3 months. * Screening score of \< 4 on the Modified Hachinski Ischemia Scale. * Women not of childbearing potential and men. * Women with negative pregnancy test prior to starting heavy water and not breastfeeding. AD * Diagnosis of probable AD. * Mild to moderate disease severity according to mini-mental state examination score (MMSE) of 16-26. * Documented cognitive decline began 6 months prior to screening. * On stable doses of approved AD medications for 2 months prior to screening. * Non-medicated AD subjects are free of AD medications for 2 months prior to screening. * Mild to moderate white matter disease and up to 2 lacunar infarcts acceptable as determined by brain MRI at screening. * Investigator determines subjects to be medically stable and physically able to complete the study. * Minimum of 6 years of education and able to read, write and communicate effectively. * Adequate hearing, vision, and language skills. * Subjects and their caregivers must agree to the dosage regimens and procedures, report for scheduled visits, and communicate with study personnel. PSP * Diagnosis of probable PSP. * Brain MRI at screening excluding potential causes of parkinsonism, especially cerebrovascular and space occupying lesions. * Mild-to-moderate stage of disease severity by a Golbe Staging System score of 1-3. * Subjects and their caregivers must agree to the dosage regimens and procedures, report for scheduled visits, and communicate with study personnel. * Currently on stable doses of PSP medications for 2 months prior to screening. * Investigator determines subjects to be medically stable and able to complete the study. * Minimum of 6 years of education and able to read, write and communicate effectively. * Adequate hearing, vision, and language skills. EHV * No clinically significant deviation from healthy for their age group. * No subjective or objective memory loss. * MMSE score of 28 to 30. Exclusion Criteria: * Diseased subjects with a medical condition (not AD or PSP) that could contribute to the subjects dementia or Parkinsonism. * History of pallidotomy, thalamotomy, active DBS or fetal tissue transplant. * Any significant acute or chronic illness. * Major surgery within 4 weeks of Day 1. * Blood/plasma donation to a blood bank or a clinical study (except a screening visit) within 4 weeks of Day 1. * Blood transfusion within 4 weeks of Day 1. * Inability to be venipunctured. * Inability to be lumbar punctured or contraindications to lumbar puncture or epidurals. * \> 10 cigarettes/day. * Recent drug or alcohol abuse or positive urine screen for drugs of abuse. * Subjects deemed inappropriate to undergo a MRI. * Any medical, psychiatric or social reason as determined by the investigator. * AD subjects with a history of CSF or amyloid imaging studies not consistent with Alzheimer's pathology. * Healthy subjects with a history of CSF or amyloid imaging studies consistent with Alzheimer's pathology. * Allergies to local anesthetics. * Any significant drug allergy.