Neuroinflammation, White Matter Integrity, AD Biomarkers and Pathology in Corticobasal Syndrome
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- The investigators will use C-11 ER176 PET imaging to evaluate neuroinflammation and white matter integrity in CBS
Study Overview
Brief Summary
The primary goal of this study is to investigate inflammation and white matter damage in corticobasal syndrome and determine whether these processes are related to each other. The investigator's will address our goal by using neuroimaging and blood plasma biomarkers, as well as molecular pathology.
Detailed Description
Corticobasal syndrome (CBS) is a neurodegenerative disorder characterized by cognitive and behavioral change, as well as asymmetric parkinsonism, dystonia, myoclonus, and limb apraxia. Emerging evidence suggests neuroinflammation plays a key role in the pathogenesis of neurodegenerative disease, including the 4R tauopathies and AD, and neuroinflammation has been linked mechanistically to damage of the white matter. The primary goal of this study is to investigate inflammation and white matter damage using imaging and blood samples.
The investigator's will use the PET ligand 11C-ER176 to assess patterns of neuroinflammation in the brain and Neurite Orientation Dispersion and Density Imaging (NODDI) to measure white matter microstructure, including axonal density and alignment. The investigator's will also investigate blood plasma metrics, including neurofilament light chain and plasma glial fibrillary acidic protein (GFAP) that measure neuroaxonal injury and astrogliosis, and inflammation and tau metrics. The investigator's will employ beta-amyloid (A) and tau (T) PET to subdivide the CBS patients into those with biomarker AD (A+T+, CBS-AD) and those without biomarker AD (CBS-4R). The investigator's will also compare these groups to disease controls with typical amnestic biomarker AD (Amn-AD) and healthy controls (HC) that have previously been recruited for other grants (existing data collected under approved IRBs).
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age 18 years or older
- •Meet possible or probable CBS criteria
Exclusion Criteria
- •Subjects will be excluded if MRI is contraindicated (due to implanted device, severe claustrophobia, etc)
- •Subjects will be excluded if they have a concurrent illnesses or structural abnormality that could account for the CBS syndrome
- •Subjects will be excluded if they have a mutation in the progranulin gene
- •Subjects will excluded if they have received anti-Aβ therapy
- •Women who are pregnant will be excluded
- •Subjects will be excluded if they are actively taking daily anti-inflammatory medications (NSAIDs, corticosteriods, etc)
- •Subjects will be excluded if they have generalized inflammatory condition and treatment with immunosuppressive, corticoid/glucocorticoid, steroidal or non-steroidal anti-inflammatory medication within 2 weeks of scanning
Arms & Interventions
Corticobasal Syndrome
patients diagnosed with cbs
Intervention: AV1451 Tau (Diagnostic Test)
Corticobasal Syndrome
patients diagnosed with cbs
Intervention: C-11 ER176 Radiotracer (Diagnostic Test)
Healthy Control
Healthy Control Volunteer
Intervention: C-11 ER176 Radiotracer (Diagnostic Test)
Healthy Control
Healthy Control Volunteer
Intervention: AV1451 Tau (Diagnostic Test)
Healthy Control
Healthy Control Volunteer
Intervention: C-11 PiB (Diagnostic Test)
Corticobasal Syndrome
patients diagnosed with cbs
Intervention: C-11 PiB (Diagnostic Test)
Outcomes
Primary Outcomes
The investigators will use C-11 ER176 PET imaging to evaluate neuroinflammation and white matter integrity in CBS
Time Frame: approximately 4-5 years into study visits
Measure whether regional patterns of ER176-PET uptake and white matter microstructure abnormalities using NODDI differ between CBS-4R, CBS-AD, Amn-AD, and HC.
Secondary Outcomes
- the investigators will use blood samples to assess inflammatory and tau blood plasma metrics in CBS.(approximately 4-5 years into study visits)
Investigators
Jennifer Whitwell
Associate Consultant II
Mayo Clinic