A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech
Year: 2021
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Authors: Keith A. Josephs, Joseph R. Duffy, Heather M. Clark, Rene L. Utianski, Edythe A. Strand, Mary M. Machulda, Hugo Botha, Peter R. Martin, Nha Trang Thu Pham, Julie Stierwalt, Farwa Ali, Marina Buciuc, Matthew Baker, Cristhoper H. Fernandez De Castro, Anthony J. Spychalla, Christopher G. Schwarz, Robert I. Reid, Matthew L. Senjem, Clifford R. Jack, Val J. Lowe, Eileen H. Bigio, Ross R. Reichard, Eric. J. Polley, Nilufer Ertekin-Taner, Rosa Rademakers, Michael A. DeTure, Owen A. Ross, Dennis W. Dickson, Jennifer L. Whitwell
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,560
Awards: PIB PET Scanning in Speech and Language Based Dementias, Longitudinal Multi-modal Imaging in Progressive Supranuclear Palsy Syndromes, A Systems Approach to Targeting Innate Immunity in AD, Harnessing Molecular Networks of Resilience for Therapeutic Discoveries in AD, The neurobiology of two distinct subtypes of neurodegenerative apraxia of speech: phenotypes of Alzheimer disease related 4-repeat tauopathies, Mayo Clinic Center for Clinical and Translational Science (CCaTS), Mayo Alzheimer's Disease Research Center, Longitudinal multi-modality imaging in non-fluent/agrammatic primary progressive aphasia
OpenAlex ID: W3173062894