The purpose of this study is to investigate changes of cerebral spinal fluid (CSF) proteins over time using continuous CSF sampling for 36 hours in elderly healthy volunteers and volunteers with mild cognitive impairment or Alzheimer's Disease.

This is a study to measure specific proteins in the cerebral spinal fluid (CSF) of healthy elderly volunteers and volunteers with mild cognitive impairment (MCI) or Alzheimer's Disease (AD). No investigational medical drug will be given to volunteers during their participation in this study. Healthy elderly volunteers will be enrolled in Part A of the study and will be randomized (assigned by chance) to 1 of 4 cohorts (groups); each cohort of volunteers will undergo a different type of CSF sampling procedure (a standard frequent CSF sampling procedure, an alternative frequency of CSF sampling procedure, or the standard frequent CSF sampling procedure with 800 mg ibuprofen administered to volunteers on Day 1, or an alternative lower frequency of CSF sampling in comparison to Cohort 1) and will have blood samples collected. Volunteers with MCI or AD will be enrolled in Part B of the study and will undergo 1 CSF sampling procedure (ie, the standard frequent CSF sampling procedure). In addition, all volunteers enrolled who consent (agree) to the pharmacogenomic component of the study, will have a blood sample collected that will allow for genetic research to help understand the link between Alzheimer's Disease biomarker profiles and specific genotypes and to have their DNA samples stored for future genetic research related to CSF proteins and Alzheimer's Disease. Participation in the pharmacogenomic research is optional for volunteers enrolled in Part A Cohort 1 to 3 but required for volunteers enrolled in Part A Cohort 5 and Part B. Participation in the DNA storage component is optional and refusal to participate will not result in ineligibility for the main part of the study. There will be no blinding in this study (ie, volunteers will know the CSF sampling procedure being performed on them). CSF and blood samples will be collected over a period of 36 hours and the maximum duration of the study will be no more than 6 weeks. During the study, volunteers will be monitored to evaluate the safety and tolerability of the CSF sampling procedures.

Inclusion Criteria:

• Healthy elderly Volunteers (Part A: age range 55 to 85 years of age, inclusive) and Volunteers with AD or MCI and a typical AD biomarker signature (Part B: age range 50 to 90 years of age, inclusive), with a body mass index (BMI) between 18 and 35 kg/m2 (inclusive) who satisfy the additional inclusion criteria specified in the study protocol will be eligible for enrollment in this study

Exclusion Criteria:

• Has a clinically significant abnormal physical or neurological examination (including fundoscopy), vital signs or 12-lead electrocardiogram (ECG) at screening
• Has a relevant history of lower back pain or scoliosis and/or major (lumbar) back surgery (microdiscectomy is allowed)
• Has a history of spontaneous, prolonged or severe bleeding with unclear origin
• Has a history of epilepsy or fits or unexplained black-out
• has any other exclusion criteria as specified in the study protocol