Mixed tau and TDP-43 pathology in a patient with unclassifiable primary progressive aphasia

Abstract

Classifying primary progressive aphasia (PPA) into variants that may predict the underlying pathology is important. However, some PPA patients cannot be classified. A 78-year-old woman had unclassifiable PPA characterized by anomia, dysarthria, and apraxia of speech without agrammatism. Magnetic resonance imaging revealed left mesial temporal atrophy and 18-flourodeoxy-glucose positron emission tomography showed left anterior temporal and posterior frontal (premotor) hypometabolism. Autopsy revealed a mixed tauopathy (argyrophilic grain disease) and transactive response-DNA-binding-protein-43 proteinopathy. Dual pathologies may explain the difficulty classifying some PPA patients and recognizing this will be important as new imaging techniques (particularly tau-positron emission tomography) are introduced and patients begin enrollment in clinical trials targeting the underlying proteinopathy.

Keywords:

• frontotemporal lobar degeneration
• primary progressive aphasia
• argyrophilic grain disease
• tau
• TDP-43

Additional information

Funding

This work was supported by the National Institutes of Health. Drs Flanagan and Vemuri have no disclosures. Dr Duffy is funded by the NIH (NIDCD). Dr Whitwell is funded by the NIH (NIDCD) and the Alzheimer’s Association. Dr Dickson is funded by the NIH. Dr Josephs is funded by the NIH.