Intervention: Bexarotene
Trial phase: Phase 2
ATC code: L01XF03 | L01XX25
SMILES: C=C(c1ccc(C(=O)O)cc1)c1cc2c(cc1C)C(C)(C)CCC2(C)C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 16
Group description: 75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
Eligibility criteria:
Inclusion Criteria:

Males or females 50 to 90 of age inclusive.
Diagnosis of probable AD according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
Willing and able to provide informed consent by either the subject or subject's legal representative.
Willing and able to comply with study visits, treatment plan, laboratory tests, brain imaging and other procedures.
Subjects must have a positive 18f-AV-45 PET scan as determined by a qualified rater.
Mini-Mental State Examinations (MMSE) score between 10-20 inclusive.
Must have a study partner who is able and willing to comply with all required study procedures.
Females must be postmenopausal.
Have at least eight years of education and should have previously (in pre-AD condition) been capable of reading, writing, and communicating effectively with others in English.
If receiving therapy with a cholinesterase inhibitor and/or memantine, the dose of these agents has been stable for at least 4 weeks prior to randomization
Normal laboratory findings at baseline including CBC, chemistry panel, serum lipids, liver functions, TSH, and vitamin B12.
Must consent to ApoE genotyping

Exclusion Criteria:

Any clinically relevant neurological disorder capable of producing a dementia syndrome including Parkinson's disease, stroke, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and others.
4 or more micro-hemorrhages (amyloid-related imaging abnormalities - hemorrhage type (ARIA-H) on baseline MRI or any evidence of amyloid-related imaging abnormalities - effusion type (ARIA-E) (Sperling et al, 2011).
History of malignancy within the past five years with the exception of basal cell or squamous cell cancer, in-situ cervical cancer, or localized prostate cancer.
History of seizure in the past three years prior to randomization
Any contraindication of having brain MRI
Any contraindication of having PET (inability to lie flat and still for the duration of the scan, intolerance to previous PET such as hypersensitivity reaction to PET ligand or imaging agent)
The subject has any unstable medical illness including hypertension, congestive heart failure, chronic obstructive pulmonary disease, renal failure, liver failure or other organ compromise.
Other clinically important abnormality on vital signs, physical examination, neurologic examination, laboratory results, or electrocardiogram (ECG) examination (e.g. Atrial fibrillation) that could compromise the study or be detrimental to the subject.
The subject has received bexarotene previously.
The subject has an allergy to bexarotene.
Has had a PET scan in the past 12 months.
Has had radiotherapy in the past year.
Have participated in an investigational drug or device study within 30 days prior to Visit 2.
Have been treated with immunomodulators to treat AD (vaccines, antibodies etc) within 6 months prior to visit 2
Unable to swallow uncrushed oral medication in capsule form
Have any condition or reason that, in the opinion of the investigator, which could interfere with the ability of the patients to participate or complete the trials, or places the patient at undue risk or complicates the interpretation of safety or efficacy data.