A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech - Two Minute Papers (Phonetics)
Two Minute Papers
https://www.nature.com/articles/s41467-021-23687-8#citeas
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.
Background
Progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome that affects spoken communication. It is characterized by the gradual loss of the ability to plan and execute voluntary movements of the speech muscles. The underlying cause of PPAOS is unknown, but it is thought to be caused by the accumulation of misfolded tau proteins in the brain.
Methods
The authors of this study investigated the molecular pathology, neurobiology, biochemistry, genetics, and neuroimaging of 32 autopsy-confirmed patients with PPAOS. They used a variety of techniques, including tau immunohistochemistry, positron emission tomography (PET), and genetic sequencing.
Findings
The authors found that the most common underlying pathology in PPAOS was corticobasal degeneration (CBD), followed by progressive supranuclear palsy (PSP). Both CBD and PSP are tauopathies, which means that they are caused by the accumulation of misfolded tau proteins in the brain. The authors also found that PPAOS patients had lower levels of tau H1 haplotype frequency than patients with other tauopathies, suggesting that tau H1 may play a protective role in PPAOS.
Conclusions
The findings of this study provide new insights into the pathobiology of PPAOS. The authors' findings suggest that CBD and PSP are the most common underlying pathologies in PPAOS, and that tau H1 may play a protective role in the development of this disease.
In addition to the findings summarized above, the authors also made the following observations:
The rate of decline in PPAOS was faster in patients with CBD than in patients with PSP.
Patients with PPAOS had greater cortical degeneration than patients with other tauopathies.
Patients with PPAOS showed different patterns of brain activation on PET scans than patients with other tauopathies.
The authors suggest that these findings may have implications for the development of new treatments for PPAOS. For example, the finding that tau H1 may play a protective role in PPAOS suggests that targeting tau H1 may be a potential therapeutic strategy. The finding that patients with PPAOS have different patterns of brain activation on PET scans suggests that new imaging techniques may be able to be used to diagnose PPAOS earlier and to monitor the progression of the disease.
This study provides important new insights into the pathobiology of PPAOS. The findings of this study may lead to the development of new treatments for this devastating disease.
The apraxia of speech, it affects us all
It can be a disease so cruel and vile
Yet in spite of its ferocity, its wrath is stilled
By the knowledge we have gained through research and science
We've learned of the molecular and genetic factors
That bring about this terrible disease
We've found in the brain regions that it can be seen
And now we know how to combat its effects
We've learned how to treat it through medicines
And the help it brings, I can assure
We've been through it, and we've come out the other side
Learning more through the years we