Tau PET Imaging in the Northern Manhattan Study of Metabolism and Mind.

1. Subject recruitment and screening procedures. Subjects will be recruited from community
dwelling persons from Northern Manhattan, men and women, aged 55 to 69 years, who have
already undergone or agreed to undergo, brain magnetic resonance imaging (MRI) and
Florbetaben positron emission tomography (PET) as part of Columbia IRB protocol AAAQ2950
(PI: Luchsinger). Recruitment of participants for these studies and all study
procedures, including brain MRI, Florbetaben PET, and tau PET, are funded by existing
grant from the National Institutes of Health awarded to PI Luchsinger (R01AG050440,
RF1AG051556-01S2, R01AG055299)

2. Imaging procedures related to 18F-MK-6240 PET. One brain MRI will be performed on each
subject using a 3 T Philips scanner. Sequences performed will include 3D T1 (MPRAGE, 180
slice 1 mm resolution, 256 x 256 voxel count) for volumetric analysis and clinical
sequences to exclude subjects with significant intracranial pathology unrelated to AD,
such as malignant brain tumor of subdural hematoma. PET scans will take place on a
Biograph mCT PET scanner (Siemens Healthcare) at the CUMC Kreitchman PET Center.
Subjects will have one PET scan with 18F-MK-6240 (injected activity up to 5 mCi = 185
MBq). PET imaging will be performed without arterial sampling. Vital signs (blood
pressure, heart rate, respiratory rate, and temperature) will be checked prior to
injection of 18F-MK-6240, then at the completion of the PET scan. 18F-MK-6240 will be
purchased from Cerveau Technologies, Inc. via a licensed production facility. Subjects
will not be informed of 18F-MK-6240 PET scan results, as this scan is used only in
research and have not yet been validated for clinical use. Subjects will be informed if
a clinically important abnormality is detected on MRI or PET imaging (e.g., brain
tumor).

3. Image processing FreeSurfer (http://surfer.nmr.mgh.harvard.edu/), the MRI software
package comprising a suite of automated tools for segmentation, reconstruction, and
derivation of regional volumes and surface-based rendering, will be used for derivation
of regions-of-interest (ROIs). Eleven ROIs will be extracted from the structural T1
image: entorhinal cortex, hippocampus, inferior temporal cortex, combined superior and
middle temporal cortex, superior parietal lobule, inferior parietal lobule, precuneus,
occipital cortex, prefrontal cortex, striatum, and thalamus. 18F-MK-6240 PET images will
be analyzed as follows: Freesurfer based ROIs will be applied to coregistered PET
images. Correction for partial volume effects using a region-based voxel-wise method92
will be applied to compare to partial volume uncorrected data. Regional time-activity
curves will be extracted from the PET scans, including cerebellum which will be used as
a reference region. Standardized uptake value ratio (SUVR) values will be calculated by
dividing SUV values for each target region by that of the cerebellum. Alternative
analytic methods such as Logan DVR and Simplified Reference Tissue Method may also be
applied to compare to SUVR data.

Inclusion Criteria:

1. Age 55 to 69 years

2. Without dementia

3. Fluent in English and/or Spanish.

4. Living in Northern Manhattan.

5. Self-identified as Hispanic, non-Hispanic Black, or non-Hispanic White.

6. Already had or agreed to have a brain MRI and Florbetaben PET.

7. Able to participate in all scheduled evaluations and to complete all required tests
and procedures.

Exclusion Criteria:

1. Dementia diagnosis

2. Certain significant medical conditions, which make study procedures of the current
study unsafe. Such serious medical conditions include uncontrolled epilepsy and
multiple serious injuries.

3. Persons with serious chronic conditions (e.g. Liver Cirrhosis, renal failure), which,
in the opinion of the investigator, could increase the risk of un-anticipated adverse
events.

4. Contraindication to MRI scanning

5. Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia,
etc.).

6. Inability to have a catheter in subject's vein for the injection of radioligand.

7. Inability to have blood drawn from subject's veins.

8. Women in the age group that we are recruiting are highly unlikely to be
pre-menopausal, and thus, highly unlikely to be menstruating. However, we will ask all
women if they are post-menopausal, and in the rare case that they are not, we will
conduct a urine pregnancy test to rule out pregnancy.

Breastfeeding women will be excluded, although we expect this situation to be rare