Probable 4‐Repeat Tauopathy Criteria Predict Brain Amyloid Negativity, Distinct Clinical Features, and FDG‐PET/MRI Neurodegeneneration Patterns in Corticobasal Syndrome

Abstract

BackgroundCorticobasal syndrome (CBS) is associated with diverse underlying pathologies, including the four‐repeat (4R)‐tauopathies. The Movement Disorders Society (MDS) criteria for progressive supranuclear palsy (PSP) proposed the novel category “probable 4R‐tauopathy” to address the phenotypic overlap between PSP and corticobasal degeneration (CBD).ObjectivesTo investigate the clinical ability of the MDS‐PSP criteria for probable 4R‐tauopathy in predicting a negative amyloid‐PET in CBS. Additionally, this study aims to explore CBS patients classified as 4R‐tauopathy concerning their clinical features and neuroimaging degeneration patterns.MethodsThirty‐two patients with probable CBS were prospectively evaluated and split into those who fulfilled or did not fulfill the 4R‐tauopathy criteria (CBS‐4RT+ vs. CBS‐4RT−). All patients underwent positron emission tomographies (PET) with [18F]fluorodeoxyglucose and [11C]Pittsburgh Compound‐B (PIB) on a hybrid PET‐MRI scanner to perform multimodal quantitative comparisons with a control group.ResultsEleven patients were clinically classified as CBS‐4RT+, and only one had a positive PIB‐PET. The CBS‐4RT+ classification had 92% specificity, 52% sensitivity, and 69% accuracy in predicting a negative PIB‐PET. The CBS‐4RT+ group presented with dysarthria and perseveration more often than the CBS‐4RT− group. Moreover, the CBS‐4RT+ group showed a prominent frontal hypometabolism extending to the supplementary motor area and striatum, and brain atrophy at the anterior cingulate and bilateral striata.ConclusionsThe 4R‐tauopathy criteria were highly specific in predicting a negative amyloid‐PET in CBS. Patients classified as 4R‐tauopathy presented distinct clinical aspects, as well as brain metabolism and atrophy patterns previously associated with tauopathies.