Mixed tau and TDP-43 pathology in a patient with unclassifiable primary progressive aphasia.
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.
a Department of Neurology, Divisions of Behavioral Neurology , Mayo Clinic , Rochester , MN , USA.
Eoin P
EP
Flanagan
b Department of Neurology, Divisions of Speech Pathology , Mayo Clinic , Rochester , MN , USA.
Joseph R
JR
Duffy
c Radiology Research , Mayo Clinic , Rochester , MN , USA.
Jennifer L
JL
Whitwell
c Radiology Research , Mayo Clinic , Rochester , MN , USA.
Prashanthi
P
Vemuri
d Department of Laboratory Medicine and Pathology , Mayo Clinic , Jacksonville , FL , USA.
Dennis W
DW
Dickson
a Department of Neurology, Divisions of Behavioral Neurology , Mayo Clinic , Rochester , MN , USA.
Keith A
KA
Josephs
D000368:Aged; D018888:Aphasia, Primary Progressive / Q000378:metabolism / Q000473:pathology*; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D057177:TDP-43 Proteinopathies / Q000378:metabolism / Q000473:pathology*; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human; D016875:tau Proteins
TDP-43; argyrophilic grain disease; frontotemporal lobar degeneration; primary progressive aphasia; tau