Evaluation of [123I] AV51 and SPECT as a Marker of Beta-amyloid Protein Deposition in Subjects With Alzheimer Disease in Comparison to Healthy Subjects

Research Plan:

General Design and Methods. The underlying goal of this study is to assess 123-I AV51 SPECT
imaging as a tool to detect ß-amyloid deposition in the brain of AD research participants and
age- and gender-matched healthy subjects. All study procedures will be conducted at the
Institute for Neurodegenerative Disorders (IND) and Molecular NeuroImaging (MNI) in New
Haven, CT. Approximately 20 patients with Alzheimers disease (AD) and 10 healthy controls
will be recruited to participate in this study. Healthy controls will be examined to ensure
that there is no evidence of neurodegenerative changes including cognitive decline. Informed
consent will be obtained for all. All subjects will undergo a screening evaluation including
baseline clinical laboratory testing, a baseline physical and neurological evaluation and
baseline cognitive evaluations. Subjects will be asked to undergo a bolus injection of 123-I
AV51. Subjects will undergo serial SPECT imaging scans and serial venous plasma sampling for
measurement of 123-I AV51 in plasma (both protein bound and free) over a period of up to 6
hours. Subjects may be asked to undergo a second imaging visit between 2 and 6 weeks
following the initial imaging visit following similar procedures to the initial imaging visit
to evaluate the reproducibility of the imaging measure using this procedure. The imaging
analyses will be performed by an image-processing specialist who will remain masked to the
procedures employed with each imaging acquisition. The primary imaging outcome measure will
be the brain regional distribution volumes expressed as a brain tissue to plasma ratio of the
radioligand, 123-I AV51. Time to the peak uptake and amplitude of the peak uptake will be
evaluated for all brain regions and the results for the AD patients and controls will be
compared. For those subjects undergoing repeat imaging visits, the data from the initial scan
will be compared to the second scan to determine which offers the reproducibility of the
imaging outcome measure.

Inclusion Criteria:

Healthy Control Subject Selection. Healthy control subjects who have no neurological
disease will be recruited for this study. The following criteria will be met for inclusion
of healthy control subjects in this study:

- The participant is 50 years or older.

- Written informed consent is obtained.

- Negative history of neurological or psychiatric illness based on evaluation by a
research physician.

- Mini-Mental Status Exam score ≥28.

- For females, non-child bearing potential or negative urine or blood pregnancy test on
day of 123-I AV51 injection.

Alzheimer's Subject Selection. Subjects who have a clinical diagnosis of mild to moderate
Alzheimer's disease will be recruited for this study. The following criteria will be met
for inclusion of AD subjects in this study:

- The participant is 50 years or older.

- Written informed consent is obtained.

- Participants have a clinical diagnosis of Alzheimer's disease based on National
Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease
and Related Disorders Association (NINCDS/ADRDA) criteria.

- Mini-Mental Status Exam score < 25.

- Modified Hachinski Ischemia Scale score of ≤ 4.

- Geriatric Depression Scales (GDS) ≤ 10.

- For females, non-child bearing potential or negative urine or blood pregnancy test on
day of 123-I AV51 injection.

Exclusion Criteria:

Healthy control subjects will be excluded from participation for the following reasons:

- The subject has a clinically significant abnormal laboratory value and/or clinically
significant unstable medical or psychiatric illness.

- The subject has any disorder that may interfere with drug absorption distribution,
metabolism, or excretion (including gastrointestinal surgery).

- The subject has evidence of clinically significant gastrointestinal, cardiovascular,
hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency,
pulmonary, or other disorder or disease.

- Pregnancy

Alzheimer's subjects will be excluded from participation for the following reasons:

- The subject has signs or symptoms of another neurodegenerative disease including
Parkinson's disease, diffuse Lewy body dementia, or history of significant
cerebrovascular disease.

- The subject has a clinically significant abnormal laboratory value and/or clinically
significant unstable medical or psychiatric illness

- The subject has any disorder that may interfere with drug absorption distribution,
metabolism, or excretion (including gastrointestinal surgery)