Pilot PET Study of Regional Cerebral Protein Synthesis in Alzheimer's

Inclusion Criteria Patients may be included in the early onset probable AD group if they: * Are males or females between 50 and 69 years of age, inclusive, with onset of symptoms before age 65; * Meet the clinical criteria of the National Institute on Aging and the Alzheimer's Association workgroup for probable AD \[25\]. They have a significant cognitive impairment, Mini Mental State Examination (MMSE) score between 10 and 24 inclusive. Imaging biomarkers (hippocampal volume and cortical amyloid deposition) will be recorded for exploratory correlational analysis with PSR, but will not be used as criteria for inclusion; * Have a caregiver who can report on their mental status and activities of daily * living (ADL); * Must have capacity and be able to give informed consent. * Willing to comply with protocol and lifestyle restrictions; * Are women of childbearing potential in whom pregnancy or breast feeding has been excluded by a standard questionnaire (Appendix 3). * Understanding of English (for questionnaires); * Participant is ambulant and capable of attending a PET scan visit as an outpatient; * Participants with female partners of child-bearing potential must agree to use one of the contraception methods listed in Protocol Section 7.5.1. This criterion must be followed from after the first PET scan until after the follow-up contact; * Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test; * Body weight ≥ 50 kg. Patients may be included in the late onset probable AD group if they: * Are males or females ≥70 years of age with onset of symptoms not before age 65; * Meet the clinical criteria of the National Institute on Aging and the Alzheimer's Association workgroup for probable AD \[25\]. They have a significant memory impairment, Mini Mental State Examination (MMSE) score between 10 and 24 inclusive. Imaging biomarkers (hippocampal volume and cortical amyloid deposition) will be recorded for exploratory correlational analysis with PSR, but will not be used as criteria for inclusion; * Have a caregiver who can report on their mental status and activities of daily living (ADL); * Must have capacity and be able to give informed consent. * Willing to comply with protocol and lifestyle restrictions; * Are women of childbearing potential in whom pregnancy or breast feeding has been excluded by a standard questionnaire (appendix).Understanding of English (for questionnaires); * Participant is ambulant and capable of attending a PET scan visit as an outpatient; * Participants with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 7.5.1. This criterion must be followed from after the first PET scan until after the follow-up contact; * Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test; * Body weight ≥ 50 kg. Subjects may be included in the older control group if they: * Are males or females between 50 and 69 years of age, inclusive; * Do not have a history of or a current clinically significant neurologic or psychiatric disease and do not have symptoms of cognitive impairment * Have a Mini Mental State Examination (MMSE) score at screening between 27 and 30, and perform normally on a memory test including delay recall memory; * Willing to comply with protocol and lifestyle restrictions; * Are women of childbearing potential in whom pregnancy or breast feeding has been excluded by a standard questionnaire (appendix).Understanding of English (for questionnaires); * Participant is ambulant and capable of attending a PET scan visit as an outpatient; * Participants with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 7.5.1. This criterion must be followed from after the first PET scan until after the follow-up contact; * Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test; * Body weight ≥ 50 kg. Subjects may be included in the young control group if they: * Are males or females between 18 and 25 years of age, inclusive; * Do not have a history of or a current clinically significant neurologic or psychiatric disease and do not have symptoms of cognitive impairment; * Do not have a first grade relative with early onset AD; * Have a Mini Mental State Examination (MMSE) score at screening between * 27 and 30, and perform normally on a memory test including delay recall memory; * Willing to comply with protocol and lifestyle restrictions; * Are women of childbearing potential in whom pregnancy or breast feeding has been excluded by a standard questionnaire (appendix).Understanding of English (for questionnaires); * Participant is ambulant and capable of attending a PET scan visit as an outpatient; * Participants with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 7.5.1. This criterion must be followed from after the first PET scan until after the follow-up contact; * Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test; * Body weight ≥ 50 kg. Exclusion Criteria: * Have a history of or a current clinically significant neurologic or psychiatric disease (other than AD); * Have a current clinically significant endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer; * Have a clinically significant infectious disease, including Acquired Immunodeficiency Syndrome (AIDS) or Human Immunodeficiency Virus (HIV) infection; * Have a recent history of alcohol or substance abuse or dependence; * Clinically significant brain injury or abnormality, other than associated with AD; * Are women of childbearing potential who are not surgically sterile, not refraining from sexual activity, or not using reliable methods of contraception (as detailed in Section 7.5.1); * Treatment with stable doses of psychotropic medication is not prohibited. In particular, patients with AD may be on a stable dose of an anticholinesterase, memantine, neuroleptic or antidepressant, and may be taking vitamin E at the time of imaging; * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); * History of or suffers from claustrophobia or participant feels unable to lie flat and still on their back for a period of up to 90 minutes in the PET scanner; * Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations or occupational exposure in the past 12 months or greater than 10 mSv in a single year including the proposed study. Clinical exposure from which the participant receives a direct benefit is not included in these calculations; * Previous inclusion in a research and/or medical protocol involving study medication within the last 3 months; * In the opinion of the study team they are unlikely to comply with the study protocol and restrictions that it imposes. ; * Contraindications for participants undergoing an MRI scan (including but not limited to metal implants pacemakers, etc.).