Journal of the neurological sciences · 2025
Low synaptic and neurosecretory proteins in cerebrospinal fluid in early parkinsonian disease.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Jakobsson Protik, Nilsson Johanna, Nygren Maria, Zetterberg Henrik, Blennow Kaj, Constantinescu Radu, Constantinescu Julius, Brinkmalm Ann, Bäckström David
Аннотация
BACKGROUND: The early pathogenesis of Parkinson's disease (PD) and the atypical parkinsonian disorders multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) is poorly understood, but presynaptic and axonal dysfunction are hypothesized to play a prominent role.
OBJECTIVE: To identify synapse- and/or axonal dysfunction as indicated by cerebrospinal fluid (CSF) biomarker profiles and their clinical correlates in early-stage PD, MSA, and PSP.
METHODS: Liquid chromatography mass spectrometry and enzyme-linked immunosorbent assay analyses of CSF samples from patients with early-stage PD (n = 38), MSA (n = 21), or PSP (n = 19), and age-matched, neurologically healthy controls (n = 30).
RESULTS: Compared to controls, patients with early parkinsonian disorders had significantly reduced CSF levels of the synapse-associated proteins neuronal pentraxin-1 (NPTX1), amyloid precursor protein, and β-amyloid 42 (Aβ42), as well as the neurosecretory granin-derived proteins secretogranin-II, chromogranin-A, and secretogranin-VII. Among these, synapse-associated proteins correlated with non-motor features, while none correlated with age. CSF levels of the predominantly axonal proteins neurofilament light (NfL) and tau were elevated in patients with MSA or PSP. Reduced NPTX1 and Aβ42 distinguished PD from PSP, while elevated NfL and tau distinguished PSP and/or MSA from PD.
CONCLUSIONS: Low CSF levels of biomarkers associated with synaptic and neurosecretory function (e.g., NPTX1) implicate age-independent synaptic dysfunction as a shared, early feature in the pathogenesis of PD, MSA, and PSP. Such biomarkers may be particularly sensitive correlates of early non-motor dysfunction. Early axonal dysfunction is more pronounced in PSP and MSA than in PD.
OBJECTIVE: To identify synapse- and/or axonal dysfunction as indicated by cerebrospinal fluid (CSF) biomarker profiles and their clinical correlates in early-stage PD, MSA, and PSP.
METHODS: Liquid chromatography mass spectrometry and enzyme-linked immunosorbent assay analyses of CSF samples from patients with early-stage PD (n = 38), MSA (n = 21), or PSP (n = 19), and age-matched, neurologically healthy controls (n = 30).
RESULTS: Compared to controls, patients with early parkinsonian disorders had significantly reduced CSF levels of the synapse-associated proteins neuronal pentraxin-1 (NPTX1), amyloid precursor protein, and β-amyloid 42 (Aβ42), as well as the neurosecretory granin-derived proteins secretogranin-II, chromogranin-A, and secretogranin-VII. Among these, synapse-associated proteins correlated with non-motor features, while none correlated with age. CSF levels of the predominantly axonal proteins neurofilament light (NfL) and tau were elevated in patients with MSA or PSP. Reduced NPTX1 and Aβ42 distinguished PD from PSP, while elevated NfL and tau distinguished PSP and/or MSA from PD.
CONCLUSIONS: Low CSF levels of biomarkers associated with synaptic and neurosecretory function (e.g., NPTX1) implicate age-independent synaptic dysfunction as a shared, early feature in the pathogenesis of PD, MSA, and PSP. Such biomarkers may be particularly sensitive correlates of early non-motor dysfunction. Early axonal dysfunction is more pronounced in PSP and MSA than in PD.