A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech.
Aged
Aged, 80 and over
Anisotropy
Apraxias
/ complications
Cognitive Dysfunction
/ complications
Diffusion Tensor Imaging
Disease Progression
Female
Fluorodeoxyglucose F18
/ chemistry
Humans
Longitudinal Studies
Male
Middle Aged
Neurobiology
Neuroimaging
Neurons
/ metabolism
Pathology, Molecular
Positron-Emission Tomography
Speech
tau Proteins
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 06 2021
08 06 2021
Historique:
received:
28
01
2021
accepted:
11
05
2021
entrez:
9
6
2021
pubmed:
10
6
2021
medline:
16
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34103532
doi: 10.1038/s41467-021-23687-8
pii: 10.1038/s41467-021-23687-8
pmc: PMC8187627
doi:
Substances chimiques
tau Proteins
0
Fluorodeoxyglucose F18
0Z5B2CJX4D
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3452Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC014942
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC012519
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061796
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062677
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002377
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS089757
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC010367
Pays : United States
Références
Neurology. 2014 May 13;82(19):1729-35
pubmed: 24727315
Stroke. 2015 Jun;46(6):1561-6
pubmed: 25908457
Neurology. 2006 Feb 14;66(3):411-4
pubmed: 16476942
Cortex. 2017 May;90:138-148
pubmed: 27771043
Brain. 2006 Jun;129(Pt 6):1385-98
pubmed: 16613895
Acta Neuropathol. 2014 Mar;127(3):397-406
pubmed: 24385136
J Med Genet. 2005 Nov;42(11):837-46
pubmed: 15792962
Neurology. 2010 Jan 5;74(1):42-9
pubmed: 19940270
Mov Disord Clin Pract. 2019 May 29;6(6):452-461
pubmed: 31392246
Mov Disord. 2017 Jun;32(6):853-864
pubmed: 28467028
J Neurol. 2020 Sep;267(9):2697-2704
pubmed: 32440921
Brain Pathol. 2021 Mar;31(2):267-282
pubmed: 33314436
Neurology. 1991 Apr;41(4):479-86
pubmed: 2011243
Neurology. 2001 Jun;56(11 Suppl 4):S16-20
pubmed: 11402145
Brain. 2011 Sep;134(Pt 9):2456-77
pubmed: 21810890
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
Eur J Neurol. 2013 Oct;20(10):1417-22
pubmed: 23746093
Brain. 1962 Dec;85:665-78
pubmed: 14026018
Hum Mol Genet. 1999 Apr;8(4):711-5
pubmed: 10072441
Neurology. 2013 May 14;80(20):1856-61
pubmed: 23616165
Aphasiology. 2020;35(4):592-613
pubmed: 33981126
PLoS One. 2014 Jul 23;9(7):e102656
pubmed: 25054218
Brain. 2019 Aug 1;142(8):2466-2482
pubmed: 31199471
Neurology. 2013 Jul 23;81(4):337-45
pubmed: 23803320
Neurocase. 2016;22(1):55-9
pubmed: 25929342
Neurology. 1994 Nov;44(11):2015-9
pubmed: 7969952
Neuroimage. 2010 Feb 1;49(3):2457-66
pubmed: 19818860
Ann Neurol. 2000 Mar;47(3):374-7
pubmed: 10716259
Arch Clin Neuropsychol. 1999 Aug;14(6):481-7
pubmed: 14590575
Neurology. 2013 Jan 29;80(5):496-503
pubmed: 23359374
Parkinsonism Relat Disord. 2020 Dec;81:34-40
pubmed: 33045651
Brain. 2008 Feb;131(Pt 2):460-72
pubmed: 18158316
Appl Neuropsychol. 2001;8(3):161-6
pubmed: 11686651
Neuron. 2011 Oct 20;72(2):245-56
pubmed: 21944778
Brain Lang. 2014 Feb;129:43-6
pubmed: 24556336
Ann Neurol. 2004 Jan;55(1):72-9
pubmed: 14705114
Neurobiol Aging. 2008 Feb;29(2):280-9
pubmed: 17097770
J Commun Disord. 2014 Sep-Oct;51:43-50
pubmed: 25092638
JAMA Neurol. 2016 Jun 1;73(6):733-42
pubmed: 27111692
Neurocase. 2005 Aug;11(4):283-96
pubmed: 16093229
Brain. 2014 Oct;137(Pt 10):2783-95
pubmed: 25113789
J Neurol Neurosurg Psychiatry. 1992 Jul;55(7):577-80
pubmed: 1640234
Am J Speech Lang Pathol. 2007 Aug;16(3):198-208
pubmed: 17666546
J Neuropathol Exp Neurol. 2002 Nov;61(11):935-46
pubmed: 12430710
J Neurol. 2015 Sep;262(9):2064-72
pubmed: 26076744
J Neurosci Methods. 1994 Aug;53(2):125-7
pubmed: 7823614
Am J Alzheimers Dis Other Demen. 2009 Oct-Nov;24(5):408-16
pubmed: 19700669
Neuroimage Clin. 2015 Mar 25;8:429-39
pubmed: 26106568
Nature. 2006 Aug 24;442(7105):916-9
pubmed: 16862116
Brain. 2004 Jul;127(Pt 7):1479-87
pubmed: 15090478
Nature. 1998 Jun 18;393(6686):702-5
pubmed: 9641683
Acta Neuropathol. 2011 Jul;122(1):111-3
pubmed: 21644037
Brain. 2012 May;135(Pt 5):1522-36
pubmed: 22382356
Neurocase. 2018 Apr;24(2):111-120
pubmed: 29799310
Brain Lang. 2018 Sep;184:54-65
pubmed: 29980072
Acta Neuropathol. 2012 Jan;123(1):1-11
pubmed: 22101365
Acta Neuropathol. 2013 Oct;126(4):537-544
pubmed: 23995422
Alzheimer Dis Assoc Disord. 2007 Oct-Dec;21(4):S23-30
pubmed: 18090419
J Mol Neurosci. 2011 Nov;45(3):384-9
pubmed: 21720721
Neurology. 2014 Jan 21;82(3):239-47
pubmed: 24353332
J Neuropathol Exp Neurol. 2006 Apr;65(4):396-405
pubmed: 16691120