The Synapse Project

• Status: Recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The overarching goal of this project is to use [C-11]UCB-J to obtain spatial information on neuronal synapse abundance and inform Alzheimer's disease (AD) progression. The investigators propose to collect longitudinal amyloid, tau, and Synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) in participants in the Wisconsin Alzheimer's Disease Research Center (ADRC) and Wisconsin Registry for Alzheimer's Prevention (WRAP) across the clinical stages of AD, including cognitively unimpaired biomarker negative, unimpaired biomarker positive, mild cognitive impairment (MCI), and dementia due to AD.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Wisconsin, Madison
• Collaborator: National Institute on Aging (NIA)

Criteria

Inclusion Criteria:

• Cognitively unimpaired adults-

• Aged 55 - 89

• Normal cognition (results of most recent testing with the source cohort indicate the participant is cognitively unimpaired as judged by consensus or expert review)

• In good general health with no conditions/medications affecting cognition or imaging

• Willing to undergo [C-11]UCB-J, [C-11]PiB, and [F-18]MK6240 PET scans

• An adequate MRI exam within 12 months prior to baseline. An MRI will be performed if not already available.

• Mild dementia and amnestic Mild Cognitive Impairment-

• Aged 50 years or older

• Abnormal cognitive status of MCI or dementia as judged by consensus or expert review using NIA-AA 2018 criteria

• MCI's must be affected in the memory domain but may also have other affected domains

• Willing to undergo [C-11]UCB-J, [C-11]PiB, and [F-18]MK6240 PET scans

• An adequate MRI exam within 12 months prior to baseline. This MRI exam will come from ADRC/WRAP studies. Clinical MRI's (ones obtained outside of the research program) will not be adequate. An MRI will be performed if not already available from within the research program.

Exclusion Criteria:

• For women, pregnant, lactating or breastfeeding, or intention to become pregnant

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

• Stable, treated chronic medical conditions like hypertension, hypercholesterolemia, diabetes mellitus, non-metastatic dermatologic or prostatic cancer, etc. are acceptable as long as they do not, in the study investigator's opinion, contribute to cognitive dysfunction or limit participation in study procedures.

• Any illness or other consideration that makes it unlikely that the subject will be able to complete the 24-month study.

• Current or prior history (within past 5 years) of significant alcohol or substance abuse as determined by the investigator.

• Psychiatric disorders that may interfere with the study including current major Axis I DSM-V disorders including but not limited to severe Major depression, current or history of bipolar I disorder, or schizophrenia.

• MRI exclusion criteria include findings from previous MRI's within the ADRC/WRAP research program that may be responsible for neurologic status of the subject such as evidence of cerebrovascular disease with multiple infarcts, infectious disease, space-occupying lesion, normal pressure hydrocephalus, CNS trauma, or any other structural abnormality that may impact cognition or image analysis, as judged by the investigator.

• MRI-incompatible implants or devices such as certain 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 that prevents completion of MRI protocol.

• Lack of decisional capacity at the time of informed consent

• Lumbar puncture exclusion criteria include: previous lumbar spine surgery, currently taking blood-thinning anti-platelet medications, taking immunosuppressive medications, currently being treated or were recently treated for an infection or virus within the last 2 to 3 months.