A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech
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Published:2021-06-08
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Josephs Keith A.ORCID, Duffy Joseph R., Clark Heather M., Utianski Rene L., Strand Edythe A., Machulda Mary M., Botha HugoORCID, Martin Peter R.ORCID, Pham Nha Trang Thu, Stierwalt Julie, Ali Farwa, Buciuc Marina, Baker Matthew, Fernandez De Castro Cristhoper H., Spychalla Anthony J., Schwarz Christopher G.ORCID, Reid Robert I.ORCID, Senjem Matthew L., Jack Clifford R.ORCID, Lowe Val J., Bigio Eileen H., Reichard Ross R., Polley Eric. J., Ertekin-Taner Nilufer, Rademakers Rosa, DeTure Michael A., Ross Owen A.ORCID, Dickson Dennis W.ORCID, Whitwell Jennifer L.
Abstract
AbstractProgressive apraxia of speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive apraxia of speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive apraxia of speech and may have consequences for development of 4R-tau targeting treatment.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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