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Corticobasal degeneration: a pathologically distinct 4R tauopathy.

Corticobasal degeneration (CBD) is a rare, progressive neurodegenerative disorder with onset in the 5(th) to 7(th) decade of life. It is associated with heterogeneous motor, sensory, behavioral and cognitive symptoms, which make its diagnosis difficult in a living patient. The etiology of CBD is unknown; however, neuropathological and genetic evidence supports a pathogenetic role for microtubule-associated protein tau. CBD pathology is characterized by circumscribed cortical atrophy with spongiosis and ballooned neurons; the distribution of these changes dictates the patient's clinical presentation. Neuronal and glial tau pathology is extensive in gray and white matter of the cortex, basal ganglia, diencephalon and rostral brainstem. Abnormal tau accumulation within astrocytes forms pathognomonic astrocytic plaques. The classic clinical presentation, termed corticobasal syndrome (CBS), comprises asymmetric progressive rigidity and apraxia with limb dystonia and myoclonus. CBS also occurs in conjunction with other diseases, including Alzheimer disease and progressive supranuclear palsy. Moreover, the pathology of CBD is associated with clinical presentations other than CBS, including Richardson syndrome, behavioral variant frontotemporal dementia, primary progressive aphasia and posterior cortical syndrome. Progress in biomarker development to differentiate CBD from other disorders has been slow, but is essential in improving diagnosis and in development of disease-modifying therapies.

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