Tau PET Imaging in the NACC Study Cohort

The investigator will conduct a tau PET scan in cognitively normal older adults enrolled in
the National Alzheimer's Coordinating Center (NACC) study at the University of Pennsylvania's
Penn Memory Center/Alzheimer's Disease Core Center (PMC/ADC).

Study Duration: 5 years. Study Center(s): Penn Memory Center/Alzheimer's Disease Core Center
at Perelman Center for Advanced Medicine, UPHS.

Objectives: To collect Tau PET imaging in cognitively normal older adults in the NACC study
to determine relationship to clinical, cognitive, and other biomarker data. In particular,
the investigator will examine relationship of tau PET to structural and functional measures
of medial temporal lobe (MTL) subregions. Findings from this study will likely provide
insight into the mechanisms and distinctions of age-related cognitive decline and that of
preclinical Alzheimer's Disease.

Number of Subjects: 100 Diagnosis and Main Inclusion Criteria Eligible subjects will be NACC
cohort participants who have received a consensus conference designation of "Cognitively
Normal." All participants must have had their annual NACC clinical and cognitive examination
within 6 months of the tau PET imaging and an MRI scan (including high resolution imaging of
medial temporal lobe regions) and amyloid PET within 6 months.

Study Design: This is a cross-sectional study using the radiotracer 18F-AV-1451 to determine
the relationship of tau pathology to both cross-sectional and longitudinal clinical and
biomarker data of NACC cohort participants who are Cognitively Normal. All subjects will
already be part of the longitudinal cohort study, known as the "NACC" cohort, of the PMC/ADC.
For the current protocol, participants will provide informed consent before beginning any
study procedures. After screening assessments, participants will undergo PET scan imaging
with 18F-AV-1451.

Study Drug Administration: Subjects will receive a single IV bolus injection target dose of
approximately 370 MBq (10 mCi ± 20%) of 18F-AV-1451 At approximately 75 minutes post dose,
scanning will begin. An approximately 30-minute acquisition (six 5 minute intervals) will be
performed.

Adverse events will be monitored continuously during the imaging session. Subjects who
experience any adverse event during an imaging session will not be discharged until the event
has resolved or stabilized.

Statistical Methodology This is a data gathering protocol to obtain molecular imaging data in
a cohort of older adults without cognitive symptoms. However, specific analyses will include
quantitative measures of 18F-AV-1451 within the medial temporal lobe (MTL) and its
relationship to volume and thickness of MTL subregions measured with high-resolution MRI.
Additional correlation and regression analyses will be performed to determine relationships
between 18F-AV-1451 and cross-sectional and longitudinal measures acquired as part of each
individuals participation in the NACC longitudinal cohort study, including, but not limited
to, MRI imaging, neurocognitive testing, demographic information, genetic data, and clinical
outcomes.

Inclusion Criteria:

- Males and females ≥ 60 years of age.

- Part of the NACC longitudinal cohort (Protocol #: 068200) of the PMC/ADCC with
consensus conference designation of cognitively normal.

- NACC longitudinal visit must be completed or scheduled to be completed within 6 months
of the 18F-AV-1451 TAU PET scan.

- A brain MRI must be performed ≤ 6 months prior to enrollment in this study and be
deemed of adequate quality that the scan may be used for study analysis, including 7
Tesla high-resolution imaging of medial temporal lobe structures.

- An amyloid PET scan ≤ 6 months prior to enrollment in this study

- Women must be post-menopausal or surgically sterile

Exclusion Criteria:

- Any medical or psychiatric conditions that, in the opinion of the investigator, would
compromise the subject's safety or successful participation in the study.

- Have evidence of structural abnormalities such as major stroke or mass on MRI that is
likely to interfere with analysis of the PET scan

- Inability to tolerate or contraindication to imaging procedures in the opinion of an
investigator or treating physician

- Have current clinically significant cardiovascular disease or clinically significant
abnormalities on screening ECG (including but not limited to Fridericia's corrected QT
(QTcF) >450 msec)

- Have a history of significant or ongoing alcohol abuse or substance abuse or
dependence based on medical record review or self-reported