@article{6ef2727c5a1d4717b9e24c464853b98b,
title = "A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech",
abstract = "Progressive 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.",
author = "Josephs, {Keith A.} and Duffy, {Joseph R.} and Clark, {Heather M.} and Utianski, {Rene L.} and Strand, {Edythe A.} and Machulda, {Mary M.} and Hugo Botha and Martin, {Peter R.} and Pham, {Nha Trang Thu} and Julie Stierwalt and Farwa Ali and Marina Buciuc and Matthew Baker and {Fernandez De Castro}, {Cristhoper H.} and Spychalla, {Anthony J.} and Schwarz, {Christopher G.} and Reid, {Robert I.} and Senjem, {Matthew L.} and Jack, {Clifford R.} and Lowe, {Val J.} and Bigio, {Eileen H.} and Reichard, {Ross R.} and Polley, {Eric J.} and Nilufer Ertekin-Taner and Rosa Rademakers and DeTure, {Michael A.} and Ross, {Owen A.} and Dickson, {Dennis W.} and Whitwell, {Jennifer L.}",
note = "Funding Information: C.R.J. serves on an independent data monitoring board for Roche, has consulted for and served as a speaker for Eisai, and consulted for Biogen, but he receives no personal compensation from any commercial entity. V.J.L. is a consultant for AVID Radiopharmaceuticals, Eisai Co. Inc., Bayer Schering Pharma, GE Healthcare, and Merck Research, and receives research support from GE Healthcare, Siemens Molecular Imaging, and AVID Radiopharmaceuticals. M.L.S. owns stocks in Align Technology, Inc., Inovio Pharmaceuticals Inc., LHC Group, Inc., Mesa Laboratories, Inc., Natus Medical Inc., and Varex Imaging Corporation. All other authors declare no competing interests. Funding Information: We wish to thank Kris Johnson, Linda Rousseau, Virginia Phillips, and Monica Casey-Castanedes for pathological support. This study was funded by the National Institutes of Health, grants R01-DC12519, R01-DC010367, R01-DC14942, R01-NS89757, and UL1TR002377. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-021-23687-8",
language = "English (US)",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}