Evaluation of [18F]MNI-1126 as an Imaging Marker for Synaptic Density Loss

The primary objective of this protocol is to examine [18F]MNI-1126 as a tool to assess
synaptic density loss.The specific objectives are:

- Examine [18F]MNI-1126 as a tool to assess synaptic density loss.

- To measure the dynamic uptake and washout of [18F]MNI-1126 in the brain using positron
emission tomography (PET) in subjects with AD, PD, and healthy volunteers.

- To measure blood metabolites of [18F]MNI-1126 and perform kinetic modeling to assess its
ability to measure synaptic density loss in the brain using the tracer plasma
concentration or a reference region as indirect input.

- To acquire safety data following injection of [18F]MNI-1126.

Inclusion Criteria (for all subjects)

- Written informed consent must be obtained before any assessment is performed.

- Female subjects must be documented by medical records or physician's note to be either
surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal
ligation) or post-menopausal for at least 1 year (i.e. 12 consecutive months with no
menses without an alternative medical cause) or, if they are of child-bearing
potential, must commit to use two methods of contraception, one of which is a barrier
method for the duration of the study.

- Male subjects and their partners of childbearing potential must commit to the use of
two methods of contraception, one of which is a barrier method for male subjects for
the study duration.

- Male subjects must not donate sperm for the study duration.

- Willing and able to cooperate with study procedures.

- For females, non-child bearing potential or negative urine pregnancy test on day of
[18F]MNI-1126 injection.

Inclusion Criteria PD subjects:

- Are males or females ≥ 30 years of age.

- Must have at least two of the following: resting tremor, bradykinesia, rigidity (must
have either resting tremor or bradykinesia); OR either asymmetric resting tremor or
asymmetric bradykinesia.

- Have Hoehn and Yahr stage ≤3.

- Have a MMSE score ≥ 22.

- PD subjects may be treated with PD symptomatic therapy on a stable dose of medications
for a period of at least 30 days prior to the [18F]MNI-1126 PET imaging visit.

- Have screening or prior DaTscan SPECT imaging demonstrating evidence of dopamine
transporter deficit based on visual read.

Healthy volunteers inclusion criteria:

- Males and females aged ≥50 years. Healthy with no clinically relevant finding on
physical examination at screening and upon reporting for the [18F]MNI-1126 imaging
visit.

- No cognitive impairment from neuropsychological battery as judged by the investigator.

- Have screening or prior ( in the last 12 months ) amyloid PET imaging demonstrating no
significant amyloid binding based on qualitative (visual read).

- No family history of Alzheimer's disease or neurological disease associated with
dementia.

- Have a CDR global score=0.

- Have an MMSE score ≥28.

Inclusion criteria for subjects with a diagnosis of probable Alzheimer's disease (AD):

- Males and females aged 50 to 80 years.

- Have probable Alzheimer's disease dementia, based on the NINCDS/ADRDA and DSM-IV
criteria, with mild severity and amnestic presentation.

- Have a CDR score ≥ 0.5 at screening.

- Have a MMSE score ≤ 28.

- Have screening or prior (in the last 12 months) amyloid PET imaging demonstrating
amyloid binding based on qualitative analysis (visual read). Amyloid PET imaging
results will be shared with participants, and scans may be used by participants for
future research use.

- A brain MRI that supports a diagnosis of AD, with no evidence of significant
neurologic pathology (see exclusion criteria).

- Medications taken for symptomatic treatment of AD must be maintained on a stable
dosage regimen for at least 30 days before screening visit.

- Signed and dated written informed consent obtained from the subject and the subject's
legally authorized representative or caregiver (if applicable).

Exclusion Criteria all subjects:

- Laboratory tests with clinically significant abnormalities and/or clinically
significant unstable medical illness.

- Subject has received an investigational drug or device within 30 days of screening

- Prior participation in other research protocols or clinical care in the last year in
addition to the radiation exposure expected from participation in this clinical study,
such that radiation exposure exceeds the effective dose of 50 mSv, which would be
above the acceptable annual limit established by the US Federal Guidelines.

- Pregnancy, lactating or breastfeeding.

- Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal,
hematological, neoplastic, endocrine, alternative neurological, immunodeficiency,
pulmonary, or other disorder or disease.

- Unsuitable veins for repeated venipuncture.

- MRI exclusion criteria include: Findings that may be responsible for the neurologic
status of the patient such as significant evidence of cerebrovascular disease (more
than two lacunar infarcts, any territorial infarct >1cm3, or deep white matter
abnormality corresponding to an overall Fazekas scale of 3 with at least one confluent
hyperintense lesion on the FLAIR sequence that is ≥20 mm in any dimension), infectious
disease, space-occupying lesions, normal pressure hydrocephalus or any other
abnormalities associated with CNS disease.

- Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps,
cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS
aneurysm clips and other medical implants that have not been certified for MRI, or
history of claustrophobia in MRI.

- Are claustrophobic or otherwise unable to tolerate the imaging procedure

Exclusion criteria for subjects with AD:

• Has received treatment that targeted Aβ or tau within the last 3 months.

Exclusion criteria for subjects PD:

- Ongoing treatment with methylphenidate, modafinil, metoclopramide, alpha methyldopa,
reserpine, or amphetamine derivative for subjects requiring DaTscan imaging.

- Subjects may take stable doses of bupropion, however this medication must be held for
at least 12 hours prior to DaTscan imaging.

- Subject has known hypersensitivity to iodine or potassium iodide (KI) in the opinion
of the Investigator.