Alzheimer's PET Imaging in Racially/Ethnically Diverse Adults

Deposition of hyperphosphorylated tau protein is observed in several neurodegenerative diseases including Alzheimer's Disease (AD), progressive supranuclear palsy, corticobasal degeneration, chronic traumatic encephalopathy, and frontotemporal lobar degeneration. Tau is a microtubular protein and its native function is to provide structural support to neurons. Paired helical filaments composed of dysfunctional tau protein are found in several neurodegenerative diseases. In AD, the clinical progression of dementia has been shown to correlate with the amount and topographical spread of tau throughout the brain. Therefore, detecting and quantifying tau aggregate load in brain would have diagnostic and prognostic potential in clinical management of several neurological diseases. As disease modifying drugs that target tau are being developed, there is a critical need for a reliable method of detecting tau aggregates to confirm pathology in patients entering clinical trials.

• 18F-MK-6240 (Drug), also known as [18F]MK-6240: Administration of 5 mCi of 18F-MK-6240 for tau PET.
• 18F-Florbetaben (Drug), also known as [18F]Florbetaben: Administration of 8.1 mCi as a slow single intravenous bolus (6 sec/mL) in a total volume of up to 10 mL of 18F-Florbetaben for Aβ PET imaging.

Primary outcomes

• Regional SUVR Value for 18F-MK-6240 [1 day]: Regional standardized uptake value ratio (SUVR) for 18F-MK-6240 will be calculated to investigate associations with measures of memory, olfactory function, and cerebrovascular disease.
• Number of Participants With Amyloid Positivity (Aβ+) for 18F-Florbetaben [1 day]: 18F-Florbetaben will be calculated to investigate the potential moderation of amyloid on the associations with tau.

Sex: All, ages: 35 Years to 85 Years, accepts healthy volunteers

Inclusion Criteria:

* Aged 35 - 85 years
* Have either mild cognitive impairment or mild clinical Alzheimer's disease; or have no problem with memory or thinking.
* Able to participate in all scheduled evaluations and to complete all required tests and procedures
* Considered likely to comply with the study protocol and to have a high probability of completing the study

Exclusion Criteria:

* Past or present history of a certain brain disease other than mild cognitive impairment or mild clinical Alzheimer's disease.
* Certain significant medical conditions. Examples are uncontrolled epilepsy or multiple serious injuries.
* Unable to lie still for PET scans.
* Radiation exposure for research studies in the last year that would put you past allowable limits if included in this study.
* Participation in the last year in a clinical trial for a disease modifying drug for AD unless it can be determined that your received placebo and not active drug.
* Conditions that preclude entry into the scanner (e.g. claustrophobia, etc.).
* Inability to have a catheter in your vein for the injection of the radioligand (dye).
* Currently pregnant or breastfeeding.

Participant flow

Outcome results

• Regional SUVR Value for 18F-MK-6240 (Primary), Mean, SUVR: All Participants 1.27 +/- 0.23
• Number of Participants With Amyloid Positivity (Aβ+) for 18F-Florbetaben (Primary), Count of participants, Participants: All Participants 12

Adverse events

Time frame: 1 day for each scan, within 24 months of each other

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2022-07-29)

• Adam M. Brickman, Ph.D., Principal investigator, Columbia University

NIH grants: 1RF1AG058067-01A1