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Updated: Mar 13, 2026
Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains
Published on: June 3, 2020
Progression of brain atrophy in PSP and CBS over 6 months and 1 year
Shubir Dutt1, Richard J Binney1, Hilary W Heuer1
1Department of Neurology (S.D., R.J.B., H.W.H., P.L., S.A., P.B., G.A.M., J.E., D.W., L.V., G.D.R., J.H.K., B.L.M., H.J.R., A.L.B.), University of California, San Francisco, Memory and Aging Center; Department of Communication Sciences & Disorders (R.J.B.), Saffran Center for Cognitive Neuroscience, Temple University, Philadelphia, PA; Tanz Centre for Research in Neurodegenerative Disease (M.C.T.), University of Toronto, Canada; Department of Neurosciences (I.L.), University of California, San Diego, La Jolla, CA; Gerontology Research Unit (S.M.M., B.C.D.), Massachusetts General Hospital, Harvard Medical School, Charlestown, MA; Departments of Epidemiology & Biostatistics (J.K.) and Radiology (N.S.), University of California, San Francisco; Department of Psychiatry and Behavioral Sciences (D.W.), Stanford University, CA; Department of Radiology (C.R.J.), Mayo Clinic, Rochester, MN.
Objective:
To examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents.
Methods:
Six- and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study. Longitudinal voxel-based morphometric analyses identified patterns of volume loss, and region-of-interest analyses examined rates of volume loss in brainstem (midbrain, pons, superior cerebellar peduncle), cortical, and subcortical regions based on previously validated atlases. Results were compared to those in a replication cohort of 226 patients with PSP with MRI data from the AL-108-231 clinical trial.
Results:
Patients with CBS exhibited greater baseline atrophy and greater longitudinal atrophy rates in cortical and basal ganglia regions than patients with PSP; however, midbrain and pontine atrophy rates were similar. Voxel-wise analyses showed distinct patterns of regional longitudinal atrophy in each group as compared to normal controls. The midbrain/pons volumetric ratio differed between diagnoses but remained stable over time. In both patient groups, brainstem atrophy rates were correlated with disease progression measured using the PSP Rating Scale.
Conclusions:
Volume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects.
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