Effect of CT1812 Treatment on Brain Synaptic Density

Inclusion Criteria:

- Participants may be included in the study only if they meet all of the following
criteria:

1. Men, and women of non-childbearing potential, 50-85 years of age inclusively,
with a diagnosis of mild to moderate Alzheimer's disease according to the 2011
NIA-AA criteria and at least a 6 month decline in cognitive function documented
in the medical record.

1. Non-childbearing potential for women is defined as postmenopausal [last
natural menses greater than 24 months; in women under age 55, menopausal
status will be documented with serum follicle stimulating hormone (FSH)
test] or undergone a documented bilateral tubal ligation or hysterectomy.

2. Male participants who are sexually active with a woman of child-bearing
potential must agree to use condoms during the trial and for 3 months after
last dose unless the woman is using an acceptable means of birth control.
Acceptable forms of birth control include abstinence, birth control pills,
or any double combination of: intrauterine device (IUD), male or female
condom, diaphragm, sponge, and cervical cap.

2. Neuroimaging (MRI) obtained during screening consistent with the clinical
diagnosis of Alzheimer's disease and without findings of significant exclusionary
abnormalities (see exclusion criteria, number 3).

3. MMSE 18-26 inclusive

4. A positive amyloid (Pittsburgh imaging compound B) scan at screening, or history
of a positive amyloid scan prior to study entry, or prior lumbar puncture with a
CSF Abeta concentration consistent with Alzheimer's disease.

5. Formal education of eight or more years.

6. Must have a caregiver who sees them at least 10 hours per week, oversees the
administration of study drug, and is willing and able to oversee administration
of study medication and participate in all clinic visits and some study
assessments. The caregiver must provide written informed consent to participate
in the study.

7. Living at home or in the community (assisted living acceptable)

8. Able to swallow CT1812 capsules.

9. Stable pharmacological treatment of any other chronic conditions for at least 30
days prior to screening.

10. Capable of providing either written informed consent or oral assent to the study
procedures and for use of protected health information [Health Insurance
Portability and Accountability Act (HIPAA) Authorization, if applicable]. If the
Participant can provide only assent, their legally authorized representative also
must provide written informed consent. Written informed consent also shall be
obtained from the responsible caregiver. All consent processes must be undertaken
in the presence of a witness and prior to any study procedures.

11. Must consent to apolipoprotein E (ApoE) genotyping.

12. Generally healthy with mobility (ambulatory or ambulatory-aided, i.e., walker or
cane), vision and hearing (hearing aid permissible) sufficient for compliance
with testing procedures.

13. Able to complete all screening evaluations.

Exclusion Criteria:

- Participants will be excluded from the study if any of the following conditions apply:

1. Hospitalization or change of chronic concomitant medication within one month
prior to screening.

2. Patients living in a continuous care nursing facility

3. Screening MRI of the brain indicative of significant abnormality, including, but
not limited to, prior hemorrhage or infarct > 1 cm3, >3 lacunar infarcts,
cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural
hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or brain tumor such
as meningioma).

4. MRI incompatible implants and other contraindications for MRI, such as pacemaker,
artificial joints, non-removable body piercings, etc. Additionally, participants
who meet the following imaging exclusion criteria will not be included in this
study:

1. Claustrophobia that will result in significant anxiety and difficulty lying
still for brain imaging (MRI or PET).

2. Participation in other research studies involving ionizing radiation within
one year of the PET scans that would cause the participant to exceed the
yearly dose limits for healthy volunteers.

3. History of IV drug use that would prevent venous access for PET tracer
injection.

4. Severe motor problems that prevent the participant from lying still for
brain imaging.

5. Severe chronic pain (e.g., as the result of rheumatoid arthritis) that would
prevent them from lying still during brain imaging.

5. Clinical or laboratory findings consistent with:

1. Other primary degenerative dementia, (dementia with Lewy bodies,
fronto-temporal dementia, Huntington's disease, Jacob-Creutzfeld Disease,
Down's syndrome, etc.)

2. Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral
sclerosis, etc.)

3. Seizure disorder

4. Other infectious, metabolic or systemic diseases affecting the central
nervous system (syphilis, present hypothyroidism, present vitamin B12 or
folate deficiency, other laboratory values) etc.)

6. A current DSM-V diagnosis of active major depression, schizophrenia or bipolar
disorder. Patients with depressive symptoms successfully managed by a stable dose
of an antidepressant are allowed entry.

7. Clinically significant, advanced or unstable disease that may interfere with
outcome evaluations, such as:

1. Chronic liver disease, liver function test abnormalities or other signs of
hepatic insufficiency (ALT, AST, total bilirubin > 1.5 x ULN)

2. Respiratory insufficiency

3. Renal insufficiency eGFR < 45 mL/min based on the CKD‐EPI formula
(https://www.questdiagnostics.com/home/physicians/egfr-calculator)Heart
disease (myocardial infarction, unstable angina, heart failure,
cardiomyopathy within six months before screening)

4. Bradycardia (<45/min.) or tachycardia (>100/min.)

5. Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg)
or hypotension (systolic <90 mm Hg and/or diastolic <60 mm Hg)

6. Uncontrolled diabetes defined by HbA1c >8

8. History of cancer within 3 years of screening with the exception of fully excised
non-melanoma skin cancers or non-metastatic prostate cancer that has been stable
for at least 6 months.

9. Seropositive for human immunodeficiency virus (HIV).

10. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B
(seropositive for Hepatitis B surface antigen [HbsAg] or anti-Hepatitis C [HCV]
antibody).

11. Clinically significant abnormalities in screening laboratory tests, including:

1. hematocrit less than 33% for males and less than 30% for females

2. absolute neutrophil cell count of 1200/uL (with the exception of a
documented history of a chronic benign neutropenia), or platelet cell count
of < 120,000/uL

3. INR >1.4 or other coagulopathy, confirmed by repeat.

12. Disability that may prevent the patient from completing all study requirements
(e.g. blindness, deafness, severe language difficulty, etc.)

13. Women who are fertile and of childbearing potential.

14. Within 4 weeks of screening visit or during the course of the study, concurrent
treatment with antipsychotic agents (except risperidone ≤1.5 mg/day, quetiapine
≤100 mg/day, olanzapine ≤5 mg/day, and aripiprazole ≤10 mg/day), antiepileptics
(except gabapentin and pregabalin for nonseizure indications), centrally active
anti-hypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine,
etc.), opiate analgesics, systemic corticosteroids, psychostimulants,
antiparkinsonian medications (except for non-parkinsonian indications) and mood
stabilizers (e.g., valproate, lithium), sedatives and anxiolytics with the
exception that use of short- to medium-acting benzodiazepines for treatment of
insomnia is permitted, however, use of sedatives or hypnotics should be avoided
for 8 hours before administration of cognitive tests.

15. Any disorder that could interfere with the absorption, distribution, metabolism
or excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease,
or liver disease.)

16. Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and
memantine

17. Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g
alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day indicated by
elevated MCV significantly above normal value at screening.

18. Suspected or known allergy to any components of the study treatments.

19. Enrollment in another investigational study or intake of investigational drug
within the previous 30 days or five half-lives of the investigational drug,
whichever is longer.

20. Previous exposure to anti Aβ vaccines

21. Exposure to passive immunotherapies for AD (e.g. monoclonal antibodies) or BACE
inhibitors within the previous 180 days.

22. Contraindication to undergoing an LP including, but not limited to: inability to
tolerate an appropriately flexed position for the time necessary to perform an
LP; international normalized ratio (INR) > 1.4 or other coagulopathy; platelet
count of < 120,000/μL; infection at the desired lumbar puncture site; taking
anti-coagulant medication within 90 days of screening (Note: low dose aspirin is
permitted); degenerative arthritis of the lumbar spine; suspected
non-communicating hydrocephalus or intracranial mass; prior history of spinal
mass or trauma.

23. Use of NSAIDs more than 2 days in within any 7-day period. Each incidence of use
must be recorded in the source and CRF.

24. Any condition, which in the opinion of the investigator or the sponsor makes the
patient unsuitable for inclusion.