The study is designed to test the relationship between measurements of brain amyloid using florbetapir F 18 PET imaging and true levels of amyloid by dissection of the brain at autopsy. Amyloid in the brain is a key feature of Alzheimer's Disease (AD).

There will be two primary analyses:

• The first primary analysis will evaluate the correlation between the blinded readers' rating of amyloid plaque density on the PET scan and the cortical amyloid plaque density at autopsy.
• The second primary analysis will evaluate the specificity of the blinded readers' rating of presence or absence of amyloid plaque density on the PET scan

For the autopsy population, subjects will be enrolled from various end-of-life (e.g. hospice / hospital / nursing home) and late-life (longitudinal studies of aging) populations. Enrollment will include subjects with various levels of cognitive status, ranging from cognitively normal through dementia. It is expected that amyloid plaque density in this elderly population will range from very low (normal aging) through moderate (e.g. cognitively normal subjects with asymptomatic amyloid deposits or mild cognitive impairment (MCI) subjects with intermediate levels of amyloid deposits) to very high (subjects with AD). The study will also enroll younger healthy subjects presumably devoid of amyloid in the specificity cohort.

Screening assessments may take place over several days and will include collection of demographic information, diagnostic interview, and safety assessments. At the time of screening, subjects or caregivers will be asked to provide consent for brain donation if they are not already enrolled in a brain donation program affiliated with this study, in addition to providing informed consent for the screening and imaging procedures in the study.

Subjects who qualify for the study will have a catheter placed for intravenous (i.v.) administration of florbetapir F 18. Subjects will receive a single i.v. bolus of 370 MBq (10 mCi) of florbetapir F 18 followed by brain PET imaging for 10 minutes duration, beginning approximately 50 minutes post-injection. Vital signs and safety labs will be obtained prior to the administration of florbetapir F 18 and at the completion of the imaging session. Adverse events will be continuously monitored during the imaging session. Subjects who experience an adverse event will not be discharged until the event has been resolved or stabilized.

Inclusion Criteria (autopsy cohort):

• Have a projected life expectancy of ≤ 6 months as determined by the principal investigator (e.g. terminal medical condition) or are already enrolled in a longitudinal study of aging with an autopsy component;
• Can tolerate a 10 minute PET scan; and
• Give informed consent for study procedures and brain donation consistent with the legal requirements of the State in which they are enrolled and the State in which they die.

Inclusion Criteria (specificity cohort):

• Cognitively and neurologically healthy males and females 18 to 40 years of age;
• Who had no known risk factors for AD, including:
• Known genetic risk factors for AD, including an ApoE ε4 allele (note: ApoE genotype was determined after enrollment and was not disclosed to healthy control subjects). Scans from subjects carrying an ApoE ε4 allele were not included in the primary specificity analysis, but were included in an exploratory analysis;
• First degree relative with a known progressive dementing disorder;
• History of cognitive decline;
• History of neurologic, neurodegenerative, or psychiatric disease;
• History of head trauma; or
• Evidence of brain abnormality on a MRI scan;
• Who performed in an age-appropriate normal range on the Wechsler Logical Memory I & II, story A;
• Who could tolerate a 10-minute PET scan; and
• Who provided informed consent before any study procedures were performed.

Exclusion Criteria:

• Have primary brain tumor, known metastases to the brain, central nervous system (CNS) lymphoma;
• Have any major, focal structural loss of brain matter;
• Are aggressively being treated with life sustaining measures (e.g. currently on respirator; receiving high dose chemotherapy);
• Have a clinically significant infectious disease, including Acquired Immune Deficiency Syndrome (AIDS), Human Immunodeficiency Virus (HIV) infection, previous positive test for hepatitis or HIV or Creutzfeldt-Jakob disease (CJD);
• Are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days;
• Have ever participated in an experimental study with an amyloid targeting agent (e.g. anti-amyloid immunotherapy, secretase inhibitor);
• Have had a radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session; or
• Are females of childbearing potential who are pregnant or not using adequate contraception.