Imaging Studies in Corticobasal Syndrome

Jennifer Whitwell80 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

Conditions

Cortico Basal Degeneration Corticobasal Syndrome

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

The investigators will use C-11 ER176 PET imaging to evaluate neuroinflammation and white matter integrity in CBS

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.

Time frame: approximately 4-5 years into study visits

Secondary Outcomes

the investigators will use blood samples to assess inflammatory and tau blood plasma metrics in CBS.

Measure whether plasma metrics differ between CBS-4R, CBS-AD, Amn-AD, and HC.